37 results on '"SUZUKI, FUJIO"'
Search Results
2. M2b macrophage polarization accompanied with reduction of long noncoding RNA GAS5.
- Author
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Ito, Ichiaki, Asai, Akira, Suzuki, Sumihiro, Kobayashi, Makiko, and Suzuki, Fujio
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MACROPHAGES , *NON-coding RNA , *GENE expression , *PHENOTYPES , *FLOW cytometry - Abstract
Macrophages (Mϕ) are highly plastic and change their functional phenotypes depending on microenvironmental signals. Recent studies have shown that microRNAs are involved in the polarization of Mϕ. In this study, we demonstrated that the phenotype of M2bMϕ [CCL1(+) IL-10(+) LIGHT(+)] switches to other phenotypes with interchangeability attained through the increased expression of growth arrest-specific 5 RNA (GAS5 RNA), a long noncoding RNA. GAS5 RNA has been described as a silencer of the CCL1 gene. Various phenotypes of Mϕ were prepared from bone marrow-derived Mϕ (BMDMϕ) after stimulation with IFNγ [M(IFNγ)/M1Mϕ], IL-4 [M(IL-4)/M2aMϕ], LPS and immobilized IgG [M(LPS + IC)/M2bMϕ], and IL-10 [M(IL-10)/M2cMϕ]. BMDMϕ cultured with medium [M(no)/quiescent Mϕ] were used as a control. As compared to Μ(no), M(IFNγ), M(IL-4) and M(IL-10), the reduced level of GAS5 RNA was shown in M(LPS + IC). CCL1 and LIGHT mRNAs (typical biomarkers of M2bMϕ) were not expressed by M(LPS + IC) transduced with a GAS5 gene using lentiviral vector. The reduction of GAS5 RNA in M(LPS + IC) was mediated by the activation of nonsense-mediated RNA decay (NMD) pathway. BMDMϕ overexpressed with GAS5 RNA after GAS5 gene transduction did not polarize to M2bMϕ even though they were stimulated with LPS and IC in combination. These results indicate that the reduction of GAS5 RNA influenced by the NMD pathway activation leads to the Mϕ polarization stimulated with LPS and IC in combination. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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3. Macrophage polarization and MRSA infection in burned mice.
- Author
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Nishiguchi, Tomoki, Ito, Ichiaki, Lee, Jong O, Suzuki, Sumihiro, Suzuki, Fujio, and Kobayashi, Makiko
- Abstract
Mortality associated with Staphylococcus aureus infection remains high during the sub‐acute phase of burn injury. In this study, we aimed to improve antibacterial resistance of sub‐acutely burned mice through macrophage polarization. Sepsis did not develop in mice at the sub‐acute phase of 5% total body surface area (TBSA) burn after being infected with methicillin‐resistant S. aureus (MRSA), and M1 macrophages (interleukin (IL)‐10−IL‐12+ inducible nitric oxide synthase+ Mφ) were isolated from these mice. In contrast, predominantly M2b macrophages (C‐C motif chemokine ligand 1 (CCL1)+IL‐10+IL‐12− Mφ) were isolated from mice with >15% TBSA burn, and all of these mice died after the same MRSA infection. Comparing NOD scid gamma mice inoculated with Mφ with 25% TBSA burns, all mice treated with CCL1 antisense oligodeoxynucleotide (ODN) survived after MRSA infection, whereas all untreated mice given the same infection died within 4 days. CCL1 antisense ODN has been characterized as a specific polarizer of M2bMφ. M1Mφ were isolated from MRSA‐infected mice with 25% TBSA burn after treatment with CCL1 antisense ODN, and these mice were shown to be resistant against a lethal dose of MRSA infection. M1Mφ were also isolated from 25% TBSA‐burned mice infected with MRSA when the ODN was administered therapeutically, and subsequent sepsis was effectively controlled in these mice. These results indicate that the M2bMφ polarizer is beneficial for controlling MRSA infection in mice at the sub‐acute phase of severe burn injury. [ABSTRACT FROM AUTHOR]
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- 2017
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4. Orosomucoid 1 drives opportunistic infections through the polarization of monocytes to the M2b phenotype.
- Author
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Nakamura, Kiwamu, Ito, Ichiaki, Kobayashi, Makiko, Herndon, David N., and Suzuki, Fujio
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OROSOMUCOID , *OPPORTUNISTIC infections , *MONOCYTES , *HUMAN phenotype , *MACROPHAGES , *ANTIBACTERIAL agents , *NATURAL immunity - Abstract
Orosomucoid (ORM, composed of two isoforms, ORM1 and ORM2) has been described as an inducer of M2 macrophages, which are cells that decrease host antibacterial innate immunities. However, it is unknown which phenotypes of M2 macrophages are induced by ORM. In this study, healthy donor monocytes stimulated with ORM (ORM-monocytes) were characterized phenotypically and biologically. CCL1 (a biomarker of M2b macrophages) and IL-10 were detected in monocyte cultures supplemented with ORM1; however, CCL17 (a biomarker of M2a macrophages) and CXCL13 (a biomarker of M2c macrophages) were not produced in these cultures. All of these soluble factors were not detected in the culture fluids of monocytes stimulated with ORM2. Monocytes stimulated with ORM1 were characterized as CD64 − CD209 − CD163 + CCL1 + cells. MRSA and Enterococcus faecalis infections were accelerated in chimeras (NOD/scid IL-2Rγ null mice reconstituted with white blood cells) after inoculation with monocytes stimulated with ORM1 or treatment with ORM1; however, the infections were greatly mitigated in both chimeras inoculated with ORM1-stimulated monocytes and treated with ORM1, after an additional treatment with an inhibitor of M2b macrophages (CCL1 antisense ODN). These results indicate that ORM1 stimulates quiescent monocytes to polarize to M2b monocytes. The regulation of M2b macrophages may be beneficial in controlling opportunistic infections in patients with a large amount of plasma ORM1. [ABSTRACT FROM AUTHOR]
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- 2015
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5. Depressed production of beta-defensins from mouse splenic dendritic cells following thermal injury and its influence on susceptibility to infection.
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Kawasaki, Takashi, Kawasaki, Chika, Sata, Takeyoshi, Kobayashi, Makiko, and Suzuki, Fujio
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DEFENSINS , *DENDRITIC cells , *IMMUNITY , *PSEUDOMONAS aeruginosa , *PSEUDOMONAS aeruginosa infections - Abstract
Purpose: Beta-defensins (BDs) and dendritic cells (DC) have been described as major effectors on host antimicrobial innate immunities. In the present study, the ability of DC to produce BDs was explored using DC from normal mice and full-thickness (FT)-burned mice. Methods: DCs were isolated from spleens of mice, and 1 × 10 cells/ml of them were cultured with LPS or SAC. Culture fluids harvested 24 h after cultivation were assayed for BD1 and BD3 and antibacterial activity (colony-counting, Pseudomonas aeruginosa). Also, DCs were tested for BD mRNAs by RT-PCR. Results: Sixty-five percent of the bacterial killing activity was shown by the culture fluids of splenic DC from normal mice, while only 15 % killing activity was shown by the culture fluids of splenic DC from FT-burned mice. X-irradiated NOD SCID IL-2rγ mice inoculated with splenic DC from FT-burned mice showed increased susceptibility to P. aeruginosa infection compared to those from normal mice. Mice splenic DC expressed BD1 mRNA constitutively and expressed BD3 mRNA after stimulation. These BDs were produced by mice splenic DC. As compared with DC from normal mice, DC from FT-burned mice produced decreased amounts of BD1 and BD3 in their culture fluids. Conclusions: These results indicate that (1) DC from spleens of mice have an ability to produce BDs, and (2) the production of BDs by DC is influenced strongly by thermally injured stress. Since FT-burned mice are susceptible to P. aeruginosa infection, BDs produced by DC may play an important role on the host's antibacterial resistance. [ABSTRACT FROM AUTHOR]
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- 2015
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6. Lineage−CD34+CD31+ Cells That Appear in Association with Severe Burn Injury Are Inhibitory on the Production of Antimicrobial Peptides by Epidermal Keratinocytes.
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Yoshida, Shohei, Lee, Jong O., Nakamura, Kiwamu, Suzuki, Sumihiro, Hendon, David N., Kobayashi, Makiko, and Suzuki, Fujio
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PSEUDOMONAS aeruginosa infections , *ANTIMICROBIAL peptides , *KERATINOCYTES , *CD34 antigen , *CELL culture , *NATURAL immunity , *HOST-parasite relationships - Abstract
Antimicrobial peptides are major host defense effectors against Pseudomonas aeruginosa skin infections. Due to the lack of such peptide production, severely burned hosts are greatly susceptible to P. aeruginosa burn wound infection. β-Defensin (HBD) production by normal human epidermal keratinocytes (NHEK) was inhibited by lineage−CD34+ cells isolated from peripheral blood of severely burned patients. Lineage−CD34+ cells obtained from severely burned patients were characterized as CD31+, while healthy donor lineage−CD34+ cells were shown to be CD31− cells. Lineage−CD34+CD31− cells did not show any inhibitory activities on HBD-1 production by NHEK. CCL2 and IL-10 released from lineage−CD34+CD31+ cells were shown to be inhibitory on the peptide production by NHEK, while these soluble factors were not produced by lineage−CD34+CD31− cells. After treatment with a mixture of mAbs for CCL2 and IL-10, the culture fluids of lineage−CD34+CD31+ cells did not show any inhibitory activities on HBD-1 production by NHEK. Lineage−CD34+CD31+ cells that appear in association with burn injuries play a role on the inhibition of antimicrobial peptide production by skin keratinocytes through the production of CCL2 and IL-10. [ABSTRACT FROM AUTHOR]
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- 2014
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7. Effect of Glycyrrhizin on Pseudomonal Skin Infections in Human-Mouse Chimeras.
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Yoshida, Shohei, Lee, Jong O., Nakamura, Kiwamu, Suzuki, Sumihiro, Hendon, David N., Kobayashi, Makiko, and Suzuki, Fujio
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KERATINOCYTES , *CHIMERISM , *LABORATORY mice , *CD34 antigen , *BLOOD testing , *SKIN diseases , *PSEUDOMONAS - Abstract
In our previous studies, peripheral blood lineage−CD34+CD31+ cells (CD31+ IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγnull mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31+ IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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8. Impaired ability of burn patient neutrophils to stimulate β-defensin production by keratinocytes.
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Kawasaki, Takashi, Nakamura, Kiwamu, Jeschke, Marc G, Kogiso, Mari, Kobayashi, Makiko, Herndon, David N, and Suzuki, Fujio
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KERATINOCYTES , *NEUTROPHILS , *BURN patients , *INTERLEUKIN-12 , *PSEUDOMONAS aeruginosa , *ENZYME-linked immunosorbent assay - Abstract
Immunosuppressive neutrophils (PMN-II) appearing in association with burn injury have a role on the increased susceptibility of burn patients to various infections. In the present study, the role of PMN-II on the production of human β-defensins (HBDs), important molecules on host antimicrobial innate immunities, by human keratinocytes was studied. Normal human epidermal keratinocytes (NHEKs) were cultured with neutrophils (PMNs) isolated from burn patients or healthy volunteers in dual-chamber transwells. Culture fluids harvested 24 h after cultivation were assayed for HBDs using enzyme-linked immunosorbent assay. Also, these culture fluids were assayed for their antimicrobial activities by a standard colony-counting method using Pseudomonas aeruginosa. In the results, PMNs isolated from peripheral blood of burn patients were confirmed as PMN-II, because these cells produced CC-chemokine ligand 2 (CCL2), but not interleukin (IL)-12 and CC-chemokine ligand 3 (CCL3). Culture fluids of NHEK transwell-cultured with healthy PMNs exhibited strong killing activities against P. aeruginosa (96% inhibition), however, the growth of bacteria was not dramatically inhibited by the culture fluids of NHEK transwell-cultured with burn-patient PMNs (36% inhibition). IL-12 and CCL3 containing culture fluids of healthy PMNs stimulated with the bacterial antigen or rCCL3 and rIL-12 enhanced the production of HBD2 and HBD3 by NHEK, whereas CCL2 containing culture fluids of burn-patient PMN stimulated with the antigen or rCCL2 inhibited the HBD production by NHEK. These results indicate that PMN-II appearing in association with burn injury contribute to the decreased production of HBDs in thermally injured patients. [ABSTRACT FROM AUTHOR]
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- 2012
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9. 331 Innate immunity: Preclinical study of eradication of tumor cells by IFN-activated monocytes in vitro and in vivo
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Baron, Samuel, Poast, Joyce, Suzuki, Fujio, Kobayashi, Makiko, Clouse, Kathleen, Bacot, Sylvia, Tiffany, Linda, Lankford, Carla, Boekhoudt, Gunther, Morrow, Angel, Fey, Samuel, Schmeisser, Hana, Bekisz, Joseph, and Zoon, Kathryn
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- 2008
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10. Effect of IL-10 antisense gene therapy in severely burned mice intradermally infected with MRSA
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Asai, Akira, Kogiso, Mari, Kobayashi, Makiko, Herndon, David N., and Suzuki, Fujio
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INTERLEUKIN-10 , *ANTISENSE drugs , *METHICILLIN-resistant staphylococcus aureus , *ABSCESSES , *SEPSIS , *LABORATORY mice , *BURNS & scalds - Abstract
Abstract: The effect of IL-10 antisense oligodeoxynucleotides (ODN) on the susceptibility of burned mice to intradermal (i.d.) infection of methicillin-resistant Staphylococcus aureus (MRSA) was studied. Abscesses formed and sepsis did not develop in normal mice infected i.d. with 108 CFU/mouse of MRSA. Similarly, sepsis caused by MRSA i.d. infection did not develop and abscesses formed in burned mice treated with IL-10 antisense ODN. However, all of the burned mice treated with scrambled ODN (control group) died by infectious complications stemming from MRSA i.d. infection, and an MRSA-abscess did not form in these mice. Macrophages (Mϕ) isolated from the infection site tissue of burned mice that were treated with IL-10 antisense ODN were identified as M1Mϕ, while Mϕ isolated from burned mice that were treated with scrambled ODN were shown to be M2Mϕ. MRSA-abscesses formed in burned mice inoculated with M1Mϕ, and these mice resisted a lethal dose of MRSA i.d. infection. However, an abscess did not form, and sepsis caused by MRSA i.d. infection developed in burned mice that were inoculated with M2Mϕ. These results indicate that severely burned mice treated with IL-10 antisense ODN are resistant against i.d. infection with MRSA. M1Mϕ appeared in the infection site tissues of severely burned mice that were treated with IL-10 antisense ODN may play a role on the abscess formation and inhibiting sepsis caused by MRSA i.d. infection. [Copyright &y& Elsevier]
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- 2012
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11. Lack of Th17 Cell Generation in Patients with Severe Burn Injuries.
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Inatsu, Akihito, Kogiso, Man, Jeschke, Marc G., Asai, Akira, Kobayashi, Makiko, Herndon, David N., and Suzuki, Fujio
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BURNS & scalds , *CANDIDA , *T cells , *BIOMARKERS , *BIOINDICATORS - Abstract
ImmunodefIcient patients with severe burn injuries are extremely susceptible to infection with Candida albicans. In addition to Thi cells, IL-17-producing CD4+ T cells (Th17 cells) have recently been described as an important effector cell in host anti-Candida resistance. In this study, therefore, we tried to induce Th17 cells in cultures of severely burned patient PBMC by stimulation with the C. albicans Ag (CAg). In the results, the biomarkers for Th17 cells (IL-17 production and intracellular expression of IL-17 and retinoic acid receptor-related orphan receptor γt) were not displayed by burn patient PBMC stimulated with CAg, whereas these biomarkers of Th17 cells were detected in cultures of healthy donor PBMC stimulated with CAg. Burn patient sera were shown to be inhibitory on CAg-stimulated Th17 cell generation in healthy donor PBMC cultures; however, Th17 cells were induced by CAg in healthy donor PBMC cultures supplemented with burn patient sera that were previously treated with anti-IL-10 mAb. Also, the biomarkers of Th17 cells were not induced by CAg in healthy donor PBMC cultures supplemented with rIL-l0. 11-10 was detected in serum specimens derived from severely burned patients. These results indicate that Th17 cells are not generated in burn patient PBMC cultures supplemented with CAg. IL-10, produced in response to burn injuries, is shown to be inhibitory on Th17 cell generation. The high susceptibility of severely burned patients to C. albicans infection might be influenced if burn associated IL-10 production is intervened. [ABSTRACT FROM AUTHOR]
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- 2011
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12. Inhibitory effect of glycyrrhizin on the neutrophil-dependent increase of R5 HIV replication in cultures of macrophages.
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Yoshida, Tsuyoshi, Kobayashi, Makiko, Xiao-Dong Li, Pollard, Richard B., and Suzuki, Fujio
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HIV , *MACROPHAGES , *NEUTROPHILS , *T cells , *MONOCLONAL antibodies - Abstract
It has been described that polymorphonuclear neutrophils (PMNs) enhance the replication of CC-chemokine receptor 5/macrophage-tropic (R5) HIV in cultures of monocyte-derived macrophages (MDMs). In this study, the inhibitory effect of glycyrrhizin (GL) on R5 HIV replication influenced by PMNs was investigated in MDM cultures. The replication of R5 HIV in MDMs was greatly enhanced when cells were co-cultured with freshly isolated PMNs (syngeneic to MDMs). When GL was added to this culture, however, the viral replication enhanced by PMNs was completely inhibited. CCL2 and interleukin 10 (IL-10) were produced in cultures of PMNs exposed to R5 HIV, and the replication of R5 HIV was greatly enhanced in MDM cultures supplemented with a mixture of recombinant CCL2 and IL-10. However, CCL2 and IL-10 were not produced by PMNs exposed to R5 HIV, when GL was added to the cultures. In the presence of GL, these soluble factors were not detected in co-cultures of MDMs and PMNs exposed to R5 HIV. In addition, the replication of R5 HIV in MDMs stimulated with CCL2 and IL-10 was not directly influenced by GL. These results indicated that GL suppresses the PMN-dependent increase of R5 HIV replication in MDMs through inhibiting CCL2/IL-10 production by PMNs stimulated with R5 HIV. [ABSTRACT FROM AUTHOR]
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- 2009
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13. Impairment of the host's antibacterial resistance by norepinephrine activated neutrophils
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Tsuda, Yasuhiro, Kobayashi, Makiko, Herndon, David N., and Suzuki, Fujio
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BIOMARKERS , *CELLS , *CULTURE , *SEPSIS - Abstract
Abstract: The susceptibility of mice to infectious complications is dramatically increased in an accompaniment with systemic inflammatory response syndrome (SIRS). Polymorphonuclear neutrophils with immunosuppressive ability (PMN-II) that appear in response to SIRS have been classified as one of the cells responsible for the increased susceptibility of mice with SIRS (SIRS mice) to sepsis induced by cecal-ligation and puncture (CLP). Since a high level of norepinephrine (NE) is demonstrated in the plasma of SIRS mice, in the present study, the role of NE on the appearance of PMN-II in SIRS mice was studied. Similar to SIRS mice, normal mice became susceptible to CLP-induced infectious complications after inoculation with NE-treated PMN. CCL2 and IL-10 (biomarkers for PMN-II) were equally produced by PMN-II prepared from SIRS mice and NE-treated PMN. However, CCL3 and IL-12 (biomarkers for immunostimulatory PMN, PMN-I) were not detected in culture fluids from either PMN preparation. These results indicate that NE mass-produced in association with SIRS development plays a role on the generation of PMN-II and the appearing PMN-II are responsible, in part, for increased susceptibility of SIRS mice to CLP-induced infectious complications. [Copyright &y& Elsevier]
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- 2008
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14. Acceleration of R5 HIV replication by polymorphonuclear neutrophils in cultures of macrophages.
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Yoshida, Tsuyoshi, Jones, Vickie C., Kobayashi, Makiko, Xiao-Dong Li, Pollard, Richard B., and Suzuki, Fujio
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CELL communication , *HIV , *VIRAL replication , *NEUTROPHILS , *MACROPHAGES , *MONOCLONAL antibodies , *CYTOLOGY - Abstract
Cell-to-cell contact between monocyte-derived macrophages (MDM) and endothelial cells has resulted in the increased proliferation of CC chemokine receptor 5/M-tropic (R5) human immunodeficiency virus (HIV) in MDM. In the present study, R5 HIV replication was shown to be increased by polymorphonuclear neutrophils (PMN) in MDM cultures through the soluble factors released from these PMN. The replication of R5 HIV in MDM was greatly enhanced when PMN were added to cultures. An increase in the replication of R5 HIV was also demonstrated when the virus was replicated in MDM cultured in a double chamber transwell with PMN. Chemokine ligand (CCL) 2 and interleukin (IL)-10 were detected in culture fluids of PMN exposed to R5 HIV. The replication of R5 HIV was not accelerated in cultures of MDM and PMN in a double chamber transwell supplemented with a mixture of monoclonal antibodies directed against CCL2 and IL-10. Similarly, the replication of R5 HIV was accelerated in MDM cultures supplemented with a mixture of recombinant CCL2 and IL-10. These results indicated that, in response to the viral stimulation, PMN produce CCL2 and IL-10 and enhance the replication of R5 HIV in MDM cultures.Immunology and Cell Biology (2007) 85, 215–219. doi:10.1038/sj.icb.7100024; published online 9 January 2007 [ABSTRACT FROM AUTHOR]
- Published
- 2007
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15. Microglial cells from psychologically stressed mice as an accelerator of cerebral cryptococcosis.
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SHIMODA, MASAE, JONES, VICKIE C., KOBAYASHI, MAKIKO, and SUZUKI, FUJIO
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NEUROGLIA , *PSYCHOLOGICAL stress , *INTRACEREBRAL hematoma , *CRYPTOCOCCUS neoformans , *MICE , *CHEMOKINES , *NATURAL immunity - Abstract
Severe stress decreases the resistance of hosts exposed to microbial infections. As compared with two groups of control mice (normal mice, food-and-water-deprived mice [FWD mice]), restraint-stressed mice (RST mice) were shown to be greatly susceptible to intracerebral growth of Cryptococcus neoformans. The susceptibility of FWD mice to cerebral cryptococcosis increased to the level shown in RST mice, when these groups of mice were inoculated with microglial cells from the brains of RST mice. However, the susceptibility of FWD mice to cerebral cryptococcosis was not influenced by the adoptive transfer of microglial cells from normal mice or FWD mice. Microglial cells from RST mice produced CC-chemokine ligand-2 (CCL-2/monocyte chemoattractant protein 1), but not microglial cells from FWD mice. The resistance of RST mice to cerebral cryptococcosis was improved to the extent shown in FWD mice, when they were treated with anti-CCL-2 antibody. However, the susceptibility of normal mice and FWD mice to cerebral cryptococcosis increased to that shown in RST mice, when they were treated with rCCL-2. Microglial cells from RST mice were discriminated from the same cell preparations derived from FWD mice by their abilities to produce CCL-2, to phagocytize C. neoformans cells and to express Toll-like receptor 2. These results indicate that the resistance of RST mice to cerebral cryptococcosis is diminished by CCL-2 produced by microglial cells that are influenced by restraint stress. [ABSTRACT FROM AUTHOR]
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- 2006
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16. Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions
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Takei, Miwa, Kobayashi, Makiko, Herndon, David N., Pollard, Richard B., and Suzuki, Fujio
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CYTOKINES , *CHEMOKINES , *IMMUNE response , *CELLULAR immunity - Abstract
Abstract: In association with the systemic inflammatory response syndrome (SIRS), anti-inflammatory response syndrome is commonly manifested in patients with trauma, burn injury, and after major surgery. These patients are increasingly susceptible to infection with various pathogens due to the excessive release of anti-inflammatory cytokines from anti-inflammatory effector cells. Recently, CC-chemokine ligand 2 (CCL2) found in the sera of mice with pancreatitis was identified as an active molecule for SIRS-associated anti-inflammatory response manifestation. Also, the inhibitory activity of glycyrrhizin (GL) on CCL2 production was reported. Therefore, the effect of GL on SIRS-associated anti-inflammatory response manifestation was investigated in a murine SIRS model. Without any stimulation, splenic T cells from mice 5 days after SIRS induction produced cytokines associated with anti-inflammatory response manifestation. However, these cytokines were not produced by splenic T cells from SIRS mice previously treated with GL. In dual-chamber transwells, IL-4-producing cells were generated from normal T cells cultured with peripheral blood polymorphonuclear neutrophils (PMN) from SIRS mice. However, IL-4-producing cells were not generated from normal T cells in transwell cultures performed with PMN from GL-treated SIRS mice. CCL2 was produced by PMN from SIRS mice, while this chemokine was not demonstrated in cultures of PMN from SIRS mice treated with GL. These results indicate that GL has the capacity to suppress SIRS-associated anti-inflammatory response manifestation through the inhibition of CCL2 production by PMN. [Copyright &y& Elsevier]
- Published
- 2006
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17. Glycyrrhizin inhibits neutrophil-associated generation of alternatively activated macrophages
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Yoshida, Tsuyoshi, Tsuda, Yasuhiro, Takeuchi, Dan, Kobayashi, Makiko, Pollard, Richard B., and Suzuki, Fujio
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NEUTROPHILS , *PATIENTS , *PHAGOCYTES , *GRANULOCYTES - Abstract
Abstract: Patients with severe burn injuries are extremely susceptible to infection, and the host''s antibacterial responses are frequently suppressed by alternatively activated macrophages (M2Mϕ), commonly demonstrated in these patients. An immunosuppressive subset of neutrophils (PMN-II), demonstrated in the peripheral blood of thermally injured patients, has been described as an inducer of M2Mϕ. In the present studies, the inhibitory effect of glycyrrhizin (GL) on M2Mϕ generation stimulated by PMN-II was examined. M2Mϕ were generated from resident Mϕ (R-Mϕ, lower chamber) after cultivation with PMN-II (upper chamber) in a dual-chamber transwell. However, M2Mϕ were not generated from R-Mϕ when the same transwell cultures were performed in the presence of GL. M2Mϕ were not generated from R-Mϕ after cultivation with PMN-II previously treated with GL, while R-Mϕ previously treated with GL converted to M2Mϕ after they were cultured with PMN-II in transwells. Interleukin-10 and CCL2 released from PMN-II were shown to be effector molecules responsible for the generation of M2Mϕ. However, these soluble factors were not produced by PMN-II treated with GL. These results indicate that GL inhibits PMN-II-stimulated M2Mϕ generation through the inhibition of CCL2/interleukin-10 production by PMN-II. [Copyright &y& Elsevier]
- Published
- 2006
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18. Role for IL-4 nonproducing NKT cells in CC-chemokine ligand 2-induced Th2 cell generation.
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FUJITA, KAZUHIKO, KOBAYASHI, MAKIKO, BRUTKIEWICZ, RANDY R., HANAFUSA, TOSHIAKI, HERNDON, DAVID N., and SUZUKI, FUJIO
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INTERLEUKIN-4 , *LABORATORY mice , *CELL differentiation , *CHEMOKINES , *LIGANDS (Biochemistry) , *T cells , *CELL culture - Abstract
NKT cells from C57Bl/6 mice are known to be the initial cellular source of IL-4 that acts as a trigger for Th2 cell differentiation. CC-chemokine ligand 2 (CCL2) has been described as an initial stimulator of IL-4 production by these cells; however, IL-4 was not produced by NKT cells from BALB/c mice even when Th2 cell responses were established in these mice. In this study, we found a new pathway for CCL2-associated Th2 cell generation in BALB/c mice. Splenic T cells from BALB/c mice produced IL-4 in response to CCL2 stimulation. However, IL-4 production was not seen in cultures of splenic T cells from CD1−/− mice (BALB/c origin), whereas, in the presence of CCL2, splenic T cells from CD1−/− mice produced IL-4 when NKT cells from wild-type mice were added. CCL2 induced IL-4 in cultures of NKT cells cocultured with naive T cells, but IL-4 was not produced by these cells cultured separately with CCL2. Interestingly, IL-4 was produced by naive T cells cocultured with NKT cells that were previously treated with CCL2 (CCL2-NKT cells). In addition, IL-4 was produced by naive T cells supplemented with a culture supernatant of CCL2-NKT cells. These results indicate that, through the production of a soluble factor(s) other than IL-4, NKT cells play a role in the CCL2-associated generation of Th2 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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19. Glycyrrhizin Inhibits R5 HIV Replication in Peripheral Blood Monocytes Treated with 1-Methyladenosine.
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Takei, Miwa, Kobayashi, Makiko, Li, Xiao-Dong, Pollard, Richard B., and Suzuki, Fujio
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- 2005
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20. Contribution of the sympathetic nervous system on the burn-associated impairment of CCL3 production
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Takahashi, Hitoshi, Kobayashi, Makiko, Tsuda, Yasuhiro, Herndon, David N., and Suzuki, Fujio
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LIGANDS (Biochemistry) , *SYMPATHETIC nervous system , *SEPSIS , *T cells - Abstract
Abstract: Previously, we have reported that the susceptibility of burned patients to infectious complications is increased when the production of CC-chemokine ligand 3 (CCL3) is impaired. In this study, the role of the sympathetic nervous system on impaired CCL3 production and antibacterial resistance following burn injuries was investigated. Normal mice were resistant (65% survival) to cecal ligation and puncture (CLP)-induced sepsis, while the same CLP killed 90% of thermally injured mice (TI-mice). However, TI-mice resisted CLP-induced sepsis (60% survival) when they were previously treated with CCL3 or sympathectomized with 6-hydroxydopamine (6-OHDA). Augmentation of host resistance against CLP-induced sepsis by 6-OHDA was abrogated by anti-CCL3 mAb treatment. Norepinephrine (NE) production was increased in circulation of TI-mice, and treatment of TI-mice with 6-OHDA resulted in the inhibition of NE secretion. CCL3 production was impaired in cultures of T cells from TI-mice or normal T cells treated with NE, even when stimulated with anti-CD3 mAb. However, CCL3 was produced by mAb-stimulated T cells from TI-mice previously treated with 6-OHDA. These results indicated that by inhibiting CCL3 production the sympathetic nervous system contributes to the increased susceptibility of TI-mice to sepsis. [Copyright &y& Elsevier]
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- 2005
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21. Role of natural killer T (NKT) cells lacking interleukin (IL)-4 producing abilities on the CC-chemokine ligand 2-associated herpes simplex virus type 1 infection in human severe combined immunodeficiency (SCID) mouse chimeras
- Author
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Fujita, Kazuhiko, Sandford, Arthur P., Kobayashi, Makiko, Hanafusa, Toshiaki, Herndon, David N., and Suzuki, Fujio
- Subjects
- *
HERPES simplex virus , *T cells , *LYMPHOCYTES , *SKIN infections - Abstract
Abstract: CC-chemokine ligand 2 (CCL2/monocyte chemoattractant protein 1) is known to have an important role on T helper type 2 (Th2) cell generation and described to induce interleukin (IL)-4 production by activated T cells. In the present study, an increase of CCL2 production in cultures of peripheral blood lymphocytes (PBL) from patients with severe thermal injuries was demonstrated. Severe combined immunodeficiency (SCID) mice reconstituted with PBL from healthy donors (PBL–SCID chimeras) were resistant to infection with herpes simplex virus type 1 (HSV-1). Treatment of these chimeras with recombinant human CCL2 resulted in an increased susceptibility to the same HSV-1 infection. However, human SCID mouse chimeras created by PBL depleted of natural killer T (NKT) cells (NKT- PBL–SCID chimeras) were resistant to HSV-1 infection, even though they were treated with CCL2. IL-4 was not detected in the sera of NKT- PBL–SCID chimeras treated with CCL2, while IL-4 was detected in the sera of PBL–SCID chimeras under the same CCL2 administration. NKT cells isolated from PBL were shown to be cells not responsible for CCL2-stimulated IL-4 production. However, in the presence of CCL2, IL-4 was detected in culture fluids of NKT cells co-cultured with naive T cells. This cytokine was produced in co-cultures of NKT cells pretreated with CCL2 (CCL2-NKT cells) and naive T cells. In addition, IL-4 production was demonstrated in transwell cultures of CCL2-NKT cells and naive T cells. These results suggest that NKT cells lacking IL-4 producing abilities contribute to the CCL2-associated increase in the susceptibility of thermally injured patients to HSV-1 infection through the induction of Th2 cell generation. [Copyright &y& Elsevier]
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- 2005
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22. Influence of systemic inflammatory response syndrome on host resistance against bacterial infections.
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Takahashi, Hitoshi, Tsuda, Yasuhiro, Takeuchi, Dan, Kobayashi, Makiko, Herndon, David N, and Suzuki, Fujio
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ANALYSIS of variance , *ANIMAL experimentation , *BACTERIAL diseases , *BIOLOGICAL models , *COMPARATIVE studies , *DISEASE susceptibility , *ENTEROCOCCUS , *IMMUNITY , *MACROPHAGES , *RESEARCH methodology , *MEDICAL cooperation , *METHICILLIN resistance , *MICE , *RESEARCH , *STAPHYLOCOCCAL diseases , *SURVIVAL analysis (Biometry) , *GRAM-positive bacterial infections , *EVALUATION research , *SYSTEMIC inflammatory response syndrome - Abstract
Objective: To determine the relationship between systemic inflammatory response syndrome (SIRS) and host innate immunities against bacterial infections.Design: Controlled animal study.Setting: University research laboratory.Subjects: Male BALB/c mice, 8-10 wks of age.Interventions: Morbidity and mortality rates of severe SIRS mice were compared with those of mild SIRS mice after infection with Enterococcus faecalis or methicillin-resistant Staphylococcus aureus (MRSA) or exposure to infectious complications induced by cecal ligation and puncture (CLP). In addition, a function of effector cells related to antibacterial innate immunities for these infections was analyzed in these two groups. Furthermore, SCIDbgMN mice (SCIDbg mice depleted of antibacterial effector cells) were reconstituted with effector cells from mild or severe SIRS mice and exposed to various infections.Measurements and Main Results: Severe SIRS mice were greatly susceptible to E. faecalis, MRSA, and CLP-induced sepsis. On the other hand, as compared with normal mice, mild SIRS mice were resistant to these infections. All of SCIDbgMN mice inoculated with peritoneal macrophages (PMphi) from severe SIRS mice died after infection with E. faecalis or MRSA, whereas all SCIDbgMN mice inoculated with PMphi from mild SIRS mice survived after the same infection. SCIDbgMN mice that were inoculated with PMphi from normal mice and exposed to E. faecalis, MRSA, or CLP survived at rates of 50%, 50%, or 60%, respectively. PMphi from mild SIRS mice exhibited typical properties for classically activated macrophages (CAMphi), whereas those from severe SIRS mice exhibited typical properties for alternatively activated macrophages (AAMphi).Conclusions: Mphi-associated host antibacterial innate immunities are greatly influenced by SIRS levels. CAMphi, effector cells for the antibacterial innate immunity against E. faecalis, MRSA, and CLP-induced sepsis, are induced in mild SIRS mice. AAMphi with no antibacterial capabilities are generated in mice with severe SIRS. Induction of CAMphi may protect severe SIRS patients against infections. [ABSTRACT FROM AUTHOR]- Published
- 2004
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23. Effect of IL-12 and soluble IL-4 receptor on the herpesvirus infection in human SCID chimeras whose Th2 cells predominate.
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Katakura, Tatsushi, Kobayashi, Makiko, Herndon, David N., and Suzuki, Fujio
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- *
CYTOKINES , *BURNS & scalds , *HERPES simplex virus , *HIV infections , *CYTOLOGY , *IMMUNOLOGY - Abstract
Th2 cytokines, commonly detected in burn patients, have been shown as inhibitors for the generation of Th1 cells that are essential for the host's resistance against herpes simplex virus type 1 (HSV-1) infection. In this study, the possibility of immunological treatment through the regulation of Th1/Th2 responses was examined in two kinds of human severe combined immunodeficiency (SCID) chimera models reflecting human immune functions. SCID mice injected with a mixture of PBMC from a healthy donor and Th2 cells experimentally generated from the same healthy PBMC (Th2 SCID chimeras) were more susceptible to HSV-1 infection when compared with SCID mice injected with healthy donor PBMC (healthy SCID chimeras). When Th2 SCID chimeras were individually treated with human IL-12 (hIL-12) or human soluble IL-4 receptor (hsIL-4R), hIFN-γ was not produced in their sera after antihuman CD3 mAb stimulation. However, hIFN-γ production in sera of Th2 SCID chimeras treated with the combination therapy of hIL-12 and hsIL-4R was recovered at levels observed in healthy SCID chimeras. When Th2 SCID chimeras infected with HSV-1 were treated with saline, hIL-12, hsIL-4R or a combination of hIL-12 and hsIL-4R, 13%, 13%, 25% or 100% of them survived, respectively. Also, Th1 responses (hIFN-γ production) were demonstrated in Th2 SCID chimeras that became resistant against HSV-1 infection after the combination treatment. These results suggest that individuals whose Th2 cells predominated may be immunologically controlled by the combination treatment between a Th1 response inducer and a Th2 response inhibitor. [ABSTRACT FROM AUTHOR]
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- 2004
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24. Three Different Neutrophil Subsets Exhibited in Mice with Different Susceptibilities to Infection by Methicillin-Resistant Staphylococcus aureus
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Tsuda, Yasuhiro, Takahashi, Hitoshi, Kobayashi, Makiko, Hanafusa, Toshiaki, Herndon, David N., and Suzuki, Fujio
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- *
NEUTROPHILS , *LABORATORY mice , *METHICILLIN resistance , *STAPHYLOCOCCUS aureus - Abstract
Neutrophils (PMN) have been described as critical effector cells in the host''s antibacterial innate immunities. However, the classification of murine PMNs remains unclear. Here, we show that in addition to normal PMN (PMN-N), there are at least two distinct subsets of PMNs (PMN-I and PMN-II) distinguished as follows: (1) cytokine and chemokine production (PMN-I, IL-12/CCL3; PMN-II, IL-10/CCL2; PMN-N, no cytokine/chemokine production), (2) macrophage activation (PMN-I, classically activated macrophages; PMN-II, alternatively activated macrophages; PMN-N, no effect on macrophage activation), (3) Toll-like receptor (TLR) expression (PMN-I, TLR2/TLR4/TLR5/TLR8; PMN-II, TLR2/TLR4/TLR7/TLR9; PMN-N, TLR2/TLR4/TLR9), and (4) surface antigen expression (PMN-I, CD49d+CD11b-; PMN-II, CD49d-CD11b+; PMN-N, CD49d-CD11b-). PMN-I was obtained from MRSA (methicillin-resistant Staphylococcus aureus)-resistant hosts, while MRSA-sensitive hosts were a source of PMN-II. PMN-N was obtained from naive mice. Anti-MRSA innate immunities might be influenced differently by these biochemically and physically distinguished PMNs. PMN-N may convert to PMN-I or PMN-II in response to host circumstance. [Copyright &y& Elsevier]
- Published
- 2004
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25. Increased norepinephrine production associated with burn injuries results in CCL2 production and type 2 T cell generation
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Takahashi, Hitoshi, Tsuda, Yasuhiro, Kobayashi, Makiko, Herndon, David N., and Suzuki, Fujio
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- *
BURNS & scalds , *T cells , *CHEMOKINES , *MACROPHAGES - Abstract
The susceptibility of thermally injured mice (TI-mice) to various infections is markedly influenced by burn-associated type 2 T cell responses, which are common with severe thermal injuries. Previously, we have reported that CC chemokine ligand 2/monocyte chemoattractant protein-I (CCL2) is produced in mice within 1 day of thermal injury, and the subsequent development of burn-associated type 2 T cell responses are triggered by this chemokine produced early after thermal injury. In this study, influence of norepinephrine (NE) on CCL2 production in mice early after thermal injury (TI) was investigated. Peripheral blood mononuclear cells (PBMC) and peritoneal macrophages (PMφ) from TI-mice produced CCL2, but the same cell preparations from normal mice did not. This chemokine was not produced by PBMC and PMφ from TI-mice previously treated with 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve termini. NE production was increased in circulation of TI-mice, and treatment of TI-mice with 6-OHDA resulted in the inhibition of NE secretion. When PBMC from normal mice were treated with NE, they acquired the ability to produce CCL2. Splenic T cells from TI-mice produced IL-4 into their culture fluids, while the cytokine was not produced by splenic T cells from TI-mice previously treated with 6-OHDA. These results indicate that NE may have an important role on early CCL2 production and the subsequent development of burn-associated type 2 T cell responses. [Copyright &y& Elsevier]
- Published
- 2004
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26. Insulin-like growth factor-I/insulin-like growth factor binding protein-3 alters lymphocyte responsiveness following severe burn
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Wolf, Steven E., Woodside, Kenneth J., Ramirez, Roque J., Kobayashi, Makiko, Suzuki, Fujio, and Herndon, David N.
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- *
INSULIN , *GROWTH factors , *CARRIER proteins , *BURNS & scalds - Abstract
: PurposeFollowing severe burn, patients are immunocompromised, making them at increased risk for infection. Exogenous growth hormone has been shown to partially restore immune function. Herein, we investigated Th1/Th2 cytokine profiles and cellular proliferation in isolated mononuclear cells after treatment with exogenous insulin-like growth factor-I (IGF-I), the indirect mediator of many growth hormone effects, in severely burned patients.: MethodsEight children and 2 adults with >20% total body surface area burns were prospectively randomized to receive either placebo or 4 mg/kg rhIGF-I/IGFBP-3 for one-week intervals (2 groups), with another group receiving placebo for both cycles. Normal children were examined for comparison. Isolated whole blood lymphocyte production of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines, and proliferative responses to specific T-cell mitogens were measured.: ResultsDepressed Th1 and exaggerated Th2 cytokine responses were seen in all burned subjects compared to non-burned controls (P < 0.05). IL-2 and IFN-γ production increased in patients treated with IGF-I/IGFBP-3 (P < 0.05). IL-4 production significantly decreased, while IL-10 levels did not change. Cytokine production did not change in those receiving two courses of placebo. Proliferative responses of isolated mononuclear cells to IL-2 as a Th1 specific mitogen increased with IGF-I/IGFBP-3 treatment (P < 0.05).: ConclusionsFollowing severe burn, a shift occurs toward a predominant Th2 phenotype. Exogenous IGF-I/IGFBP-3 treatment partially reverses this response. [Copyright &y& Elsevier]
- Published
- 2004
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27. Soluble IL-4 receptor improves the skin-graft-associated cytomegalovirus infection in thermally injured mice
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Kobayashi, Hiroyuki, Kobayashi, Makiko, Takahashi, Hitoshi, Herndon, David N., Pollard, Richard B., and Suzuki, Fujio
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- *
CYTOMEGALOVIRUS diseases , *T cells , *BURNS & scalds - Abstract
The susceptibility of thermally injured mice (TI-mice) to murine cytomegalovirus (MCMV) infection is markedly influenced by burn-associated type 2 T cell responses, which are common with severe thermal injuries. In the present study, the effect of soluble IL-4 receptor (sIL-4R) on the skin-graft-associated MCMV infection was investigated. The marked growth of MCMV was demonstrated in the salivary glands of TI-mice grafted with MCMV seropositive [MCMV sero(+)] skin. However, the growth of MCMV was not demonstrated in the salivary glands of TI-mice grafted with MCMV sero(+) skin and treated with 50 ng per mouse of sIL-4R. Compared with grafted normal mice, production of type 1 cytokines was markedly decreased when splenic T cells from TI-mice grafted with MCMV sero(+) skin were stimulated with anti-CD3 monoclonal antibody (mAb). The impaired type 1 cytokine production was recovered in cultures of splenic T cells from grafted TI-mice previously treated with sIL-4R. After grafting with MCMV sero(+) skin, the growth of MCMV was markedly inhibited in the salivary glands of severe combined immunodeficient (SCID) mice inoculated with T cells from TI-mice treated with sIL-4R. These results suggest that sIL-4R regulates the skin-graft-associated MCMV infection in TI-mice. [Copyright &y& Elsevier]
- Published
- 2003
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28. Therapeutic effects of IL-12 combined with benzoylmesaconine, a non-toxic aconitine-hydrolysate, against herpes simplex virus type 1 infection in mice following thermal injury
- Author
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Kobayashi, Makiko, Takahashi, Hitoshi, Herndon, David N., Pollard, Richard B., and Suzuki, Fujio
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- *
BURNS & scalds , *HERPES simplex virus , *BURNS & scalds complications , *IMMUNOMODULATORS , *ALKALOIDS , *ANIMALS , *HERPESVIRUS diseases , *INTERFERONS , *INTERLEUKINS , *MICE , *T cells , *VIRUSES , *THERAPEUTICS ,THERAPEUTIC use of alkaloids - Abstract
IL-12 is an inducer of type 1 T cell responses, which are essential in host defense against herpes simplex virus type 1 (HSV-1) infection. However, type 1 T cell responses are not elicited by IL-12 in thermally injured mice (TI-mice) that routinely have a predominance of burn-associated type 2 T cell responses. In our previous studies, benzoylmesaconine (BEN, an aconitine derivative extracted from heated-Aconiti tuber) induced the generation of CD4+ T cells antagonistic to type 2 T cells (BEN-CD4+ T cells). In the present study, the effects of a combination therapy using IL-12 and BEN to treat severe HSV-1 infection in TI-mice were investigated. When TI-mice were treated with either IL-12 (500 U per mouse) or BEN (1 μg/kg) alone, they did not resist HSV-1 infection. However, 60–80% of TI-mice exposed to HSV-1 survived after they received IL-12 and BEN or BEN-CD4+ T cells in combination. After stimulation with anti-CD3 mAb in vitro, IFN-γ was not produced in cultures of splenic T cells from TI-mice exposed to HSV-1 and treated with either IL-12, BEN or BEN-CD4+ T cell alone. However, IFN-γ production was induced by the mAb stimulation in the cultures of T cells from infected mice treated with IL-12 and BEN or BEN-CD4+ T cells in combination. These results suggest that the combination therapy of IL-12 (an inducer of type 1 T cell responses) and BEN (an inhibitor of type 2 T cell responses) may protect TI-mice from severe HSV-1 infection. [Copyright &y& Elsevier]
- Published
- 2003
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29. A Combination Therapy Using IL-12 and Soluble IL-4 Receptor on Herpes Simplex Virus Type 1 Infection in a Human–SCID Chimera Model of Thermal Injury
- Author
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Katakura, Tatsushi, Kobayashi, Makiko, Fujita, Kazuhiko, Herndon, David N., Pollard, Richard B., and Suzuki, Fujio
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- *
HERPES simplex virus , *CYTOKINES , *LYMPHOCYTES - Abstract
Herpes simplex virus type 1 (HSV-1) is a severe pathogen in thermally injured patients. Type 1 T cells are essential for the host''s anti-HSV protective immunity. Type 2 cytokines, commonly detected in thermally injured patients, have been described as inhibitors for the type 1 T cell generation. Therefore, the antiviral effects of combination therapy with a type 1 T cell inducer [interleukin (IL)-12] and a type 2 T cell inhibitor [soluble IL-4 receptor (sIL-4R)] were investigated in severe combined immunodeficiency (SCID) mice inoculated with peripheral blood lymphocytes (PBL) of thermally injured patients. Patient PBL–SCID chimeras (SCID mice inoculated with patient PBL) were susceptible to infection with 1 × 103 PFU/kg of HSV-1 (0% survival), while healthy PBL–SCID chimeras (SCID mice inoculated with PBL from healthy donors) were resistant (92% survival). When patient PBL–SCID chimeras exposed to HSV-1 were treated with saline, human recombinant (r) IL-12 or human sIL-4R, 0, 0, or 12.5% of them survived, respectively. However, 75% of these chimeras survived when they were treated with rIL-12 and sIL-4R in combination. These results indicate that HSV-1 infection in patient PBL–SCID chimeras was therapeutically controlled by the inducer of type 1 T cell responses and the inhibitor of type 2 T cell responses in combination. [Copyright &y& Elsevier]
- Published
- 2002
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30. Effect of a combination therapy between IL-12 and soluble IL-4 receptor (sIL-4R) on Candida albicans and herpes simplex virus type 1 infections in thermally injured mice.
- Author
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Kobayashi, Makiko, Takahashi, Hitoshi, Herndon, David N, Pollard, Richard B, and Suzuki, Fujio
- Subjects
- *
INTERLEUKINS , *INTERLEUKIN-12 , *INTERLEUKIN-4 , *HERPES simplex virus , *MONOCLONAL antibodies , *MICE - Abstract
The effectiveness of a combination using IL-12 and soluble IL-4 receptor (sIL-4R) to treat severe infections of herpes simplex virus type 1 (HSV-1) and Candida albicans in thermally injured mice was investigated. Although sIL-4R decreased burn-associated type 2 T-cell responses, the effect of sIL-4R was minimal on the morbidity and mortality of thermally injured mice exposed to 250 times LD[sub 50] of HSV-1 or 10 times LD[sub 50] of C. albicans. Compared with 100% mortality in control mice, mortality for HSV-1 and C. albicans was 40 and 20%, respectively, in thermally injured mice that received IL-12 and sIL-4R in combination. After stimulation with anti-CD3 monoclonal antibody, splenic T cells from thermally injured mice exposed to large amounts of HSV-1 or C. albicans did not produce gamma interferon (IFN-γ) into their culture fluids. However, IFN-γ was produced by splenic T cells from thermally injured and infected mice treated with IL-12 and sIL-4R in combination. These results suggest that therapeutic treatment with a combination of IL-12 and sIL-4R may be effective by inducing type 1 T-cell responses in thermally injured mice exposed to large amounts of HSV-1 or C. albicans.Key words: burn, IL-12, soluble IL-4 receptor, herpesvirus, Candida albicans.Nous avons évalué l'efficacité d'une combinaison d'IL-12 et de récepteur de l'IL-4 soluble (sIL-4R) pour le traitement d'infections graves par le virus de l'herpes simplex de type 1 (HSV-1) et par Candida albicans, chez des souris ayant subi des blessures thermiques. Bien que le sIL-4R a diminué les réponses de cellules T de type 2 associées aux brûlures chez les souris blessées thermiquement, il a eu peu d'impact sur la morbidité et la mortalité de souris blessées thermiquement exposées à 250 fois LD[sub 50] de HSV-1 ou à 10 fois LD[sub 50] de C. albicans. Par rapport à une mortalité de 100 % dans les souris témoins, la mortalité pour le HSV-1 et C. albicans était respectivement de 40 et de 20 % chez des souris blessées thermiquement qui ont reçu une combinaison d'IL-12 et de sIL-4R. Après une stimulation avec des mAc anti-CD3, les cellules T spléniques de souris blessées thermiquement exposées à de fortes doses de HSV-1 ou de C. albicans n'ont pas produit d'interféron gamma (IFN-γ) dans leurs milieux de culture. Toutefois, de l'IFN-γ fut produit par les cellules T spléniques de souris blessées et infectées qui avaient été traitées avec de l'IL-12 et du sIL-4R en combinaison. Ces résultats indiquent qu'une thérapie incorporant une combinaison d'IL-12 et de sIL-4R pourrait s'avérer efficace, celle-ci favorisant des réponses de cellules T de type 1 chez des souris ayant subi des blessures thermiques et ayant été exposées à de grandes quantités de HSV-1 ou de C. albicans.Mots clés : brûlures, IL-12, récepteur de l'IL-4 soluble, virus de l'herpès, Candida albicans.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]
- Published
- 2002
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31. Effect of Glycyrrhizin, an Active Component of Licorice Roots, on HIV Replication in Cultures of Peripheral Blood Mononuclear Cells from HIV-Seropositive Patients.
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Sasaki, Hidetaka, Takei, Miwa, Kobayashi, Makiko, Pollard, Richard B., and Suzuki, Fujio
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- 2002
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32. Effects of Z-100, a Mycobacterium-tuberculosis-Derived Arabinomannan, on the LP-BM5 Murine Leukemia Virus Infection in Mice.
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Sasaki, Hidetaka, Kobayashi, Makiko, Pollard, Richard B., and Suzuki, Fujio
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- 2001
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33. The regulation of burn-associated infections with herpes simplex virus type 1 or Candida....
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KOBAYASHI, MAKIKO, KOBAYASHI, HIROYUKI, MORI, KAZUYA, POLLARD, RICHARD B, SUZUKI, FUJIO, and Suzuki
- Subjects
- *
T cells , *HERPES simplex virus , *CYTOKINES - Abstract
In the accompanying paper, the resistance to infections with HSV type 1 (HSV-1) and Candida albicans was improved in thermally injured mice treated with benzoylmesaconine (BEN), an aconitine-hydrolysate isolated from heated Aconiti tuber, or inoculated with splenic CD4+ T cells from BEN-treated mice (BEN T cells). In this paper, therefore, the antiviral mechanism of BEN T cells (or BEN) on the improved resistance of burned mice to the HSV-1 infection was studied. Burn-associated CD8+ CD11b+ TCRγ/δ+ type-2 T cells have been shown to be a key on the increased susceptibility of thermally injured mice to infection with HSV-1 or C. albicans. The susceptibility of T6S-mice, mice inoculated with 1 × 106 cells/mouse of T6S cells (a clone of burn-associated type-2 T cells), to HSV-1 infection was similar to that of thermally injured mice. The adoptive transfer of BEN T cells to T6S-mice restores their impaired resistance to HSV-1 infection. The type-2 cytokine levels in sera of T6S-mice were decreased after inoculation of BEN T cells. BEN T cells inhibited the type-2 cytokine production by T6S cells when they were cocultured in vitro. BEN T cells, characterized as CD4+ CD28+ TCRα/β+ Vicia villosa (VV) lectin-adherent T cells, showed non-specific ability to inhibit the cytokine production by various type-2 T cells. From the results of the cytokine-producing profile, BEN T cells were shown to be a different subset of CD4+ T cells from Th1 and Th2 cells, although these three CD4+ T cells had similar properties phenotypically. BEN T cells were induced in normal mice 1–4 days after the oral treatment of BEN (1 μg/kg or more). These results suggest that, through the induction of antagonistic CD4+ T cells against burn-associated type-2 T cells, BEN may improve the resistance of T6S-mice (or thermally injured mice) to the... [ABSTRACT FROM AUTHOR]
- Published
- 1998
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34. The regulation of burn-associated infections with herpes simplex virus type 1 or Candida....
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KOBAYASHI, MAKIKO, MORI, KAZUYA, KOBAYASHI, HIROYUKI, POLLARD, RICHARD B, SUZUKI, FUJIO, and Suzuki
- Subjects
- *
BURNS & scalds , *HERPES simplex virus , *CANDIDA albicans - Abstract
As compared with normal unburned mice, thermally injured mice have been shown to be 50–100 times more susceptible to HSV type 1 (HSV-1) or Candida albicans infection. Benzoylmesaconine (BEN) improved the resistance of thermally injured mice against infection with HSV-1 or C. albicans to the level observed in normal mice. Mortality rates of normal mice exposed to lethal amounts of these pathogens were not affected by the BEN treatment, while significant survival effects were produced in these mice after treatment with acyclovir (against HSV-1) or amphotericin B (against C. albicans). Benzoylmesaconine did not inhibit the growth of these pathogens in vitro and did not directly reduce the viability of the pathogens. However, burned mice inoculated with CD4+ T cells from BEN-treated mice resisted infections from these pathogens. These results suggested that, through the generation of CD4+ T cells, BEN recovered the impaired resistance of thermally injured mice to infection by HSV-1 or C. albicans. [ABSTRACT FROM AUTHOR]
- Published
- 1998
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35. Stimulation of DNA synthesis in quiescent rabbit chondrocytes in culture by limited exposure to somatomedin-like growth factors.
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Hiraki, Yuji, Kato, Yukio, Inoue, Hiroyuki, and Suzuki, Fujio
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CARTILAGE cells , *SOMATOMEDIN , *DNA , *FIBROBLAST growth factors , *EPIDERMAL growth factor , *CELLS - Abstract
Cartilage-derived factor (CDF), extracted from fetal bovine cartilage, and multiplication-stimulating activity (MSA) stimulated DNA synthesis in quiescent rabbit costa! chondrocytes in culture under serum-free conditions. As described previously, when added in the presence of fibroblast growth factor (FGF) or epidermal growth factor (EGF) a somatomedin-like growth factor, CDF or MSA, synergistically stimulated DNA synthesis in the cultured chondrocytes. The present study showed that exposure of the cells to MSA or CDF for only the initial 5 h was sufficient for transmission of their full stimulatory effect. Furthermore, the limited exposure did not alter the time course of stimulation of DNA synthesis: [3H]thymidine incorporation into DNA began to increase after 16 h and reached a maximum after 24 h. In contrast to the somatomedin-like growth factors, FGF and EGF' were required continuously in the culture medium during traverse of the entire G1 phase for stimulation of DNA synthesis, and the mitogenic effects of FGF and EGF in cultured chondrocytes were stronger than those of CDF and MSA. Synergistic stimulation of DNA synthesis by CDF or MSA in the presence of FGF or EGF could be observed as long as FGF or EGF was continuously present, even when CDF or MSA was withdrawn after the first 5 h of culture. These findings suggest that, in contrast to FGF and EGF, somatomedin-like growth factors affect an early distinct stage in the ft phase of chondrocytes. [ABSTRACT FROM AUTHOR]
- Published
- 1986
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36. Differential and Synergistic Actions of Somatomedin-Like Growth Factors, Fibroblast Growth Factor and Epidermal Growth Factor in Rabbit Costal Chondrocytes.
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Kato, Yukio, Hiraki, Yuji, Inoue, Hiroyuki, Kinoshita, Masahiko, Yutani, Yasutaka, and Suzuki, Fujio
- Subjects
- *
EPIDERMAL growth factor , *DNA , *CARTILAGE cells , *RNA , *CELL division , *PROTEOGLYCANS - Abstract
Epidermal growth factor (EGF) stimulated DNA synthesis, RNA synthesis and cell division of rabbit costa! chondrocytes in culture, but did not stimulate nor inhibit proteoglycan synthesis. Multiplication-stimulating activity (MSA) and cartilage-derived factor (CDF) with somatomedin-like activity had relatively small effects on DNA synthesis and cell division of chondrocytes, but markedly enhanced the synthesis of sulfated proteoglycans. MSA and EGF had additive or synergistic effects on the growth of rabbit chondrocytes. MSA and fibroblast growth factor (FGF) also had additive or synergistic effects on the growth of rabbit chondrocytes. CDF mimicked these effects of MSA; CDF and MSA had similar stimulatory effects on DNA synthesis in rabbit chondrocytes even in the presence of EGF, FGF or both. MSA and CDF did not reduce the concentrations of EGF and FGF required for maximum stimulation of DNA synthesis. In addition, EGF and FOE had additive effects on DNA synthesis and cell division of rabbit costal chondrocytes in culture. These findings suggest that the somatomedin-like factors. EUF and PCJF have complementary effects in chondrocytes and provide further evidence that CDF produced by chondrocytes resembles somatomedin in its biological action in chondrocytes. [ABSTRACT FROM AUTHOR]
- Published
- 1983
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37. Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC.
- Author
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Asai, Akira, Tsuchimoto, Yusuke, Ohama, Hideko, Fukunishi, Shinya, Tsuda, Yasuhiro, Kobayashi, Makiko, Higuchi, Kazuhide, and Suzuki, Fujio
- Subjects
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LIVER cancer , *MACROPHAGES , *DRUG resistance in cancer cells , *PHYSIOLOGY - Abstract
Despite major advances in curative and palliative approaches, hepatocellular carcinoma (HCC) is still the third leading cause of cancer-related death worldwide. M1 macrophages (Mφ) play a key role in host antitumor defenses in HCC. In our study, CD14+cells were isolated from the peripheral blood of four groups of HCC patients (group-1, patients with stage 0 HCC; group-2, patients with stage A HCC; group-3, patients with stage B HCC; and group-4, patients with stage C HCC) and characterized phenotypically. Then, CD14+cells from group-2 and group-3 HCC patients were induced to polarize and tested for their antitumor abilities in a chimera model of HCC patients. Human HCCs (HepG2 solid tumors) grew in a chimera model of group-3 patients (group-3 HCC chimeras) but not in a chimera model of group-2 patients (group-2 HCC chimeras). In response to HCC antigens, the majority of CD14+cells from group-2 patients (group-2 CD14+cells) switched to the M1 phenotype (IL-12+IL-10−iNOS+cells), whereas the majority of CD14+cells from group-3 patients (group-3 CD14+cells) did not switch to the M1 phenotype and continued to express M2b phenotypic properties (IL-12−IL-10+CCL1+iNOS−cells). Group-3 CD14+cells showed M1Mφ polarization after treatment with CCL1 antisense oligodeoxynucleotide (ODN). Therefore, our study indicates that anti-HCC defenses of group-3 HCC chimeras are improved after CCL1 antisense ODN treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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