144 results on '"Arakaki, Rieko"'
Search Results
102. Critical role of cathepsin-inhibitors for autoantigen processing and autoimmunity
- Author
-
Ishimaru, Naozumi, primary, Arakaki, Rieko, additional, Katunuma, Nobuhiko, additional, and Hayashi, Yoshio, additional
- Published
- 2004
- Full Text
- View/download PDF
103. Prevention and Induction of Autoimmune Exocrinopathy Is Dependent on Pathogenic Autoantigen Cleavage in Murine Sjögren’s Syndrome
- Author
-
Saegusa, Kaoru, primary, Ishimaru, Naozumi, additional, Yanagi, Kumiko, additional, Mishima, Kenji, additional, Arakaki, Rieko, additional, Suda, Takashi, additional, Saito, Ichiro, additional, and Hayashi, Yoshio, additional
- Published
- 2002
- Full Text
- View/download PDF
104. Down-Regulation of CXCR4 by Human Herpesvirus 6 (HHV-6) and HHV-7
- Author
-
Yasukawa, Masaki, primary, Hasegawa, Atsuhiko, additional, Sakai, Ikuya, additional, Ohminami, Hideki, additional, Arai, Junko, additional, Kaneko, Shin, additional, Yakushijin, Yoshihiro, additional, Maeyama, Kazutaka, additional, Nakashima, Hideki, additional, Arakaki, Rieko, additional, and Fujita, Shigeru, additional
- Published
- 1999
- Full Text
- View/download PDF
105. Lipoteichoic Acid Acts as an Antagonist and an Agonist of Lipopolysaccharide on Human Gingival Fibroblasts and Monocytes in a CD14-Dependent Manner
- Author
-
Sugawara, Shunji, primary, Arakaki, Rieko, additional, Rikiishi, Hidemi, additional, and Takada, Haruhiko, additional
- Published
- 1999
- Full Text
- View/download PDF
106. Marked Increase in Anti-HIV Activity, as Well as Inhibitory Activity against HIV Entry Mediated by CXCR4, Linked to Enhancement of the Binding Ability of Tachyplesin Analogs to CXCR4
- Author
-
Xu, Younong, primary, Tamamura, Hirokazu, additional, Arakaki, Rieko, additional, Nakashima, Hideki, additional, Zhang, Xiaoyan, additional, Fujii, Nobutaka, additional, Uchiyama, Takashi, additional, and Hattori, Toshio, additional
- Published
- 1999
- Full Text
- View/download PDF
107. T134, a Small-Molecule CXCR4 Inhibitor, Has No Cross-Drug Resistance with AMD3100, a CXCR4 Antagonist with a Different Structure
- Author
-
Arakaki, Rieko, primary, Tamamura, Hirokazu, additional, Premanathan, Mariappan, additional, Kanbara, Kenji, additional, Ramanan, Sivasundaram, additional, Mochizuki, Katsura, additional, Baba, Masanori, additional, Fujii, Nobutaka, additional, and Nakashima, Hideki, additional
- Published
- 1999
- Full Text
- View/download PDF
108. A Low-Molecular-Weight Inhibitor against the Chemokine Receptor CXCR4: A Strong Anti-HIV Peptide T140
- Author
-
Tamamura, Hirokazu, primary, Xu, Younong, additional, Hattori, Toshio, additional, Zhang, Xiaoyan, additional, Arakaki, Rieko, additional, Kanbara, Kenji, additional, Omagari, Akane, additional, Otaka, Akira, additional, Ibuka, Toshiro, additional, Yamamoto, Naoki, additional, Nakashima, Hideki, additional, and Fujii, Nobutaka, additional
- Published
- 1998
- Full Text
- View/download PDF
109. A lipoteichoic acid fraction ofEnterococcus hiraeactivates cultured human monocytic cells via a CD14-independent pathway to promote cytokine production, and the activity is inhibited by serum components
- Author
-
Arakaki, Rieko, primary, Sugawara, Shunji, additional, Nakashima, Hideki, additional, Kotani, Shozo, additional, and Takada, Haruhiko, additional
- Published
- 1998
- Full Text
- View/download PDF
110. Pharmacophore identification of a chemokine receptor (CXCR4) antagonist, T22 ([Tyr 5,12 , Lys 7 ]-polyphemusin II), which specifically blocks T cell-line-tropic HIV-1 infection
- Author
-
Tamamura, Hirokazu, primary, Imai, Makoto, additional, Ishihara, Tsunehito, additional, Masuda, Masao, additional, Funakoshi, Hanae, additional, Oyake, Hiromi, additional, Murakami, Tsutomu, additional, Arakaki, Rieko, additional, Nakashima, Hideki, additional, Otaka, Akira, additional, Ibuka, Toshiro, additional, Waki, Michinori, additional, Matsumoto, Akiyoshi, additional, Yamamoto, Naoki, additional, and Fujii, Nobutaka, additional
- Published
- 1998
- Full Text
- View/download PDF
111. Effective lowly cytotoxic analogs of an HIV-cell fusion inhibitor, T22 ([Tyr5,12, Lys7]-polyphemusin II)
- Author
-
Tamamura, Hirokazu, primary, Arakaki, Rieko, additional, Funakoshi, Hanae, additional, Imai, Makoto, additional, Otaka, Akira, additional, Ibuka, Toshiro, additional, Nakashima, Hideki, additional, Murakami, Tsutomu, additional, Waki, Michinori, additional, Matsumoto, Akiyoshi, additional, Yamamoto, Naoki, additional, and Fujii, Nobutaka, additional
- Published
- 1998
- Full Text
- View/download PDF
112. Convenient one-pot synthesis of cystine-containing peptides using the trimethylsilyl chloride–dimethyl sulfoxide/trifluoroacetic acid system and its application to the synthesis of bifunctional anti-HIV compounds 1
- Author
-
Tamamura, Hirokazu, primary, Ishihara, Tsunehito, additional, Oyake, Hiromi, additional, Imai, Makoto, additional, Otaka, Akira, additional, Ibuka, Toshiro, additional, Arakaki, Rieko, additional, Nakashima, Hideki, additional, Murakami, Tsutomu, additional, Waki, Michinori, additional, Matsumoto, Akiyoshi, additional, Yamamoto, Naoki, additional, and Fujii, Nobutaka, additional
- Published
- 1998
- Full Text
- View/download PDF
113. Distribution pattern of HNF-3beta proteins in developing embryos of two mammalian species, the house shrew and the mouse
- Author
-
Yasui, Kinya, primary, Sasaki, Hiroshi, additional, Arakaki, Rieko, additional, and Uemura, Masanori, additional
- Published
- 1997
- Full Text
- View/download PDF
114. Induction of Rapid T Cell Death and Phagocytic Activity by Fas-Deficient Ipr Macrophages.
- Author
-
Oura, Ritsuko, Arakaki, Rieko, Yamada, Akiko, Kudo, Yasusei, Tanaka, Eiji, Hayashi, Yoshio, and Ishimaru, Naozumi
- Subjects
- *
T cells , *CELL death , *PHAGOCYTOSIS , *MACROPHAGES , *APOPTOSIS , *LIGANDS (Biochemistry) - Abstract
Peripheral T cells are maintained by the apoptosis of activated T cells through the Fas-Fas ligand system. Although it is well known that normal T cells fail to survive in the Fas-deficient immune condition, the molecular mechanism for the phenomenon has yet to be elucidated. In this study, we demonstrate that rapid cell death and clearance of normal T cells were induced by Fas-deficient Ipr macrophages. Transfer of normal T cells into Ipr mice revealed that Fas expression on donor T cells was promptly enhanced through the IFN-Ɣ/IFN-ƔR. In addition, Fas ligand expression and phagocytic activity of Ipr macrophages were promoted through increased NF-KB activation. Controlling Fas expression on macrophages plays an essential role in maintaining T cell homeostasis in the peripheral immune system. Our data suggest a critical implication to the therapeutic strategies such as transplantation and immunotherapy for immune disorder or autoimmunity related to abnormal Fas expression. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
115. Cathepsin L Inhibition Prevents Murine Autoimmune Diabetes via Suppression of CD8+ T Cell Activity.
- Author
-
Yamada, Akiko, Ishimaru, Naozumi, Arakaki, Rieko, Katunuma, Nobuhiko, and Hayashi, Yoshio
- Subjects
DIABETES ,AUTOIMMUNE diseases ,T cells ,CYCLOPHOSPHAMIDE ,ANTIRHEUMATIC agents ,ANTINEOPLASTIC agents ,GENES ,RNA ,NUCLEIC acids - Abstract
Background: Type 1 diabetes (T1D) is an autoimmune disease resulting from defects in central and peripheral tolerance and characterized by T cell-mediated destruction of islet β cells. To determine whether specific lysosomal proteases might influence the outcome of a T cell-mediated autoimmune response, we examined the functional significance of cathepsin inhibition on autoimmune T1D-prone non-obese diabetic (NOD) mice. Methods and Findings: Here it was found that specific inhibition of cathepsin L affords strong protection from cyclophosphamide (CY)-induced insulitis and diabetes of NOD mice at the advanced stage of CD8
+ T cell infiltration via inhibiting granzyme activity. It was discovered that cathepsin L inhibition prevents cytotoxic activity of CD8+ T cells in the pancreatic islets through controlling dipeptidyl peptidase I activity. Moreover, the gene targeting for cathepsin L with application of in vivo siRNA administration successfully prevented CY-induced diabetes of NOD mice. Finally, cathepsin L mRNA expression of peripheral CD8+ T cells from NOD mice developing spontaneous T1D was significantly increased compared with that from control mice. Conclusions: Our results identified a novel function of cathepsin L as an enzyme whose activity is essential for the progression of CD8+ T cell-mediated autoimmune diabetes, and inhibition of cathepsin L as a powerful therapeutic strategy for autoimmune diabetes. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
116. CCR7 with S1P1Signaling through AP-1 for Migration of Foxp3+Regulatory T-Cells Controls Autoimmune Exocrinopathy
- Author
-
Ishimaru, Naozumi, Yamada, Akiko, Nitta, Takeshi, Arakaki, Rieko, Lipp, Martin, Takahama, Yousuke, and Hayashi, Yoshio
- Abstract
Forkhead box p3-positive (Foxp3+) regulatory T cells (Tregcells) participate in maintaining peripheral immune tolerance and suppressing autoimmunity. We recently reported that in situpatrolling by C-C-chemokine receptor 7 (CCR7)+Tregcells in target organs is essential for controlling autoimmune lesions in Sjögren's syndrome. In the present study, the molecular mechanism underlying CCR7-mediated Tregcell migration was investigated in a mouse model. The impaired migratory response of Ccr7−/−Tregcells to sphingosine 1-phosphate (S1P) occurred because of defective association of S1P receptor 1 (S1P1) with a G coupled–protein. In addition, T-cell receptor (TCR)- and S1P1-mediated Ras-related C3 botulinum toxin substrate 1 (Rac-1), extracellular signal-related kinase (ERK), and c-Jun phosphorylation required for activator protein 1 (AP-1) transcriptional activity were significantly impaired in Ccr7−/−Tregcells. Surprisingly, the abnormal nuclear localization of Foxp3 was detected after abrogation of the c-Jun and Foxp3 interaction in the nucleus of Ccr7−/−Tregcells. These results indicate that CCR7 essentially controls the migratory function of Tregcells through S1P1-mediated AP-1 signaling, which is regulated through its interaction with Foxp3 in the nucleus.
- Published
- 2012
- Full Text
- View/download PDF
117. A lipoteichoic acid fraction of Enterococcus hirae activates cultured human monocytic cells via a CD14-independent pathway to promote cytokine production, and the activity is inhibited by serum components.
- Author
-
Arakaki, Rieko, Sugawara, Shunji, Nakashima, Hideki, Kotani, Shozo, and Takada, Haruhiko
- Published
- 1998
- Full Text
- View/download PDF
118. Analysis of in VivoRole of α-Fodrin Autoantigen in Primary Sjögren's Syndrome
- Author
-
Miyazaki, Katsushi, Takeda, Noriaki, Ishimaru, Naozumi, Omotehara, Fumie, Arakaki, Rieko, and Hayashi, Yoshio
- Abstract
The α-fodrin N-terminal portion (AFN) autoantigen mediates in vivoimmunoregulation of autoimmune responses in primary Sjögren's syndrome (SS). We further examined this process and found that cleavage products of AFN were frequently detected in the salivary gland duct cells of SS patients. In in vitrostudies using human salivary gland HSY cells, anti-Fas-induced apoptosis resulted in specific cleavage of α-fodrin into the 120-kd fragment, in association of α-fodrin with μ-calpain, and activation of caspase 3. Significant proliferative responses against AFN autoantigen were observed in the peripheral blood mononuclear cells (PBMCs) from SS patients with higher pathological score (grade 4) and with short duration from onset (within 5 years). In vivoroles of AFN peptides were investigated using PBMCs from patients with SS, systemic lupus erythematosus, and rheumatoid arthritis. Significant proliferative T-cell responses of PBMCs to AFN peptide were detected in SS but not in systemic lupus erythematosus or rheumatoid arthritis. AFN peptide induced Th1-immune responses and accelerated down-regulation of Fas-mediated T-cell apoptosis in SS. Our data further elucidate the in vivorole of AFN autoantigen on the development of SS and suggest that the AFN autoantigen is a novel participant in peripheral tolerance.
- Published
- 2005
- Full Text
- View/download PDF
119. A lipoteichoic acid fraction of Enterococcus hiraeactivates cultured human monocytic cells via a CD14‐independent pathway to promote cytokine production, and the activity is inhibited by serum components
- Author
-
Arakaki, Rieko, Sugawara, Shunji, Nakashima, Hideki, Kotani, Shozo, and Takada, Haruhiko
- Abstract
To elucidate the cellular activation mechanisms of lipoteichoic acid (LTA) compared with those of lipopolysaccharide (LPS), a quantitatively major LTA fraction, QM‐1M, was prepared from hot phenol‐water extracts of Enterococcus hirae(ATCC 9790) by hydrophobic octyl‐Sepharose chromatography and by ion‐exchange membrane (QMA‐Mem Sep 1010) chromatography as a 60% 1‐propanol‐ and 1 M NaCl‐eluted fraction. Unlike the reference Escherichia coliLPS, QM‐1M did not demonstrate any ability to induce cytokines in a human whole blood culture system in this study, whereas QM‐1M induced a few cytokines such as interleukin (IL)‐8 and tumor necrosis factor‐α in human monocytic THP‐1 cell and human peripheral mononuclear cell (PBMC) cultures in the absence of serum. Fetal calf and human sera decreased the above cytokine induction by QM‐1M in THP‐1 and PBMC cultures, whereas sera increased activities of the reference LPS. IL‐8 induction in the absence of serum in response to QM‐1M was demonstrated to proceed through a CD14‐independent pathway unlike the reference LPS.
- Published
- 1998
- Full Text
- View/download PDF
120. Pharmacophore identification of a chemokine receptor (CXCR4) antagonist, T22 ([Tyr5,12, Lys7]-polyphemusin II), which specifically blocks T cell-line-tropic HIV-1 infection
- Author
-
Tamamura, Hirokazu, Imai, Makoto, Ishihara, Tsunehito, Masuda, Masao, Funakoshi, Hanae, Oyake, Hiromi, Murakami, Tsutomu, Arakaki, Rieko, Nakashima, Hideki, Otaka, Akira, Ibuka, Toshiro, Waki, Michinori, Matsumoto, Akiyoshi, Yamamoto, Naoki, and Fujii, Nobutaka
- Abstract
We have previously found that T22 ([Tyr5,12, Lys7]-polyphemusin II) has strong anti-human immunodeficiency virus (HIV) activity, and that T22 inhibits T cell-line-tropic HIV-1 infection mediated by CXCR4/fusin. T22 is an 18-residue peptide amide, which takes an antiparallel β-sheet structure that is maintained by two disulfide bridges. Structure–activity relationship (SAR) studies on T22 have disclosed the contributions of each region of T22 to activity or cytotoxicity, and have provided the following useful information to develop new CXCR4 antagonists: The number of Arg residues in the N-terminal and C-terminal regions of T22 is closely related to anti-HIV activity. Addition of a variety of functional groups at the N-terminal end results in increases in activity. Disulfide rings, especially the major disulfide loop, are indispensable for anti-HIV activity and maintenance of the β-sheet structure. Trp3can be replaced by other aromatic residues (Tyr, Phe and l-2-naphthylalanine). Between two repeats of Tyr-Arg-Lys, which are a characteristic structure in T22, Tyr-Arg-Lys in the N-terminal portion is more closely associated with anti-HIV activity and maintenance of the β-sheet structure. A positive charge in the side chain at the (i+1) position of the β-turn region is necessary for strong activity. Through these studies, we have found several compounds having higher selectivity indexes (50% cytotoxic concentration/50% effective concentration) than that of T22.
- Published
- 1998
- Full Text
- View/download PDF
121. Interleukin-1β is a potent growth inhibitor of adult rat hepatocytes in primary culture
- Author
-
Nakamura, Toshikazu, primary, Arakaki, Rieko, additional, and Ichihara, Akira, additional
- Published
- 1988
- Full Text
- View/download PDF
122. Triphenyltetrazolium and its derivatives are anisotropic inhibitors of energy transduction in oxidative phosphorylation in rat liver mitochondria
- Author
-
Higuti, Tomihiko, primary, Arakaki, Rieko, additional, Kotera, Yasuo, additional, Takigawa, Michio, additional, Tani, Isamu, additional, and Shibuya, Masayuki, additional
- Published
- 1983
- Full Text
- View/download PDF
123. Effective lowly cytotoxic analogs of an HIV-cell fusion inhibitor, T22 ([Tyr 5,12, Lys 7]-polyphemusin II)
- Author
-
Tamamura, Hirokazu, Arakaki, Rieko, Funakoshi, Hanae, Imai, Makoto, Otaka, Akira, Ibuka, Toshiro, Nakashima, Hideki, Murakami, Tsutomu, Waki, Michinori, Matsumoto, Akiyoshi, Yamamoto, Naoki, and Fujii, Nobutaka
- Published
- 1998
- Full Text
- View/download PDF
124. Prognostic value of partial EMT‐related genes in head and neck squamous cell carcinoma by a bioinformatic analysis.
- Author
-
Kisoda, Satoru, Shao, Wenhua, Fujiwara, Natsumi, Mouri, Yasuhiro, Tsunematsu, Takaaki, Jin, Shengjian, Arakaki, Rieko, Ishimaru, Naozumi, and Kudo, Yasusei
- Subjects
- *
BLOOD coagulation factors , *CELL differentiation , *CELL lines , *CELL receptors , *GENE expression , *HEAD & neck cancer , *POLYMERASE chain reaction , *SQUAMOUS cell carcinoma , *TUMOR markers , *PHENOTYPES , *BIOINFORMATICS , *CANCER genes , *LOG-rank test - Abstract
Objective: Recent studies have revealed that the ability of cancer cells to undergo intermediate state of epithelial‐to‐mesenchymal transition (EMT), partial EMT (p‐EMT), poses a higher metastatic risk rather than complete EMT. Here, we examined the prognostic value of p‐EMT‐related genes in head and neck squamous cell carcinoma (HNSCC) by bioinformatic approaches. Materials and methods: We used RNA‐seq data of 519 primary HNSCC cases obtained from TCGA database. We compared the expression of p‐EMT‐related genes in HNSCC tissues with normal tissues. We evaluated the prognostic value of p‐EMT‐related genes in HNSCC cases by log‐rank test. We examined the expression of p‐EMT‐, EMT‐, and epithelial differentiation‐related genes by qPCR. Results: Among p‐EMT‐related genes that were highly expressed in HNSCC cases, high expression of SERPINE1, ITGA5, TGFBI, P4HA2, CDH13, and LAMC2 was significantly correlated with poor survival of HNSCC patients. By gene expression pattern, HNSCC cell lines were classified into three groups: epithelial phenotype, EMT phenotype, and p‐EMT phenotype. Conclusions: Our findings suggest that p‐EMT program may be involved in poor prognosis of HNSCC. SERPINE1, ITGA5, TGFBI, P4HA2, CDH13, and LAMC2 can be used for a prognostic marker. Moreover, HNSCC cells with p‐EMT phenotype can be a useful model for investigating a nature of p‐EMT. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
125. IL-10 and CXCL2 in trigeminal ganglia in neuropathic pain.
- Author
-
Iwasa, Takuma, Afroz, Shaista, Inoue, Miho, Arakaki, Rieko, Oshima, Masamitsu, Raju, Resmi, Waskitho, Arief, Inoue, Masahisa, Baba, Otto, and Matsuka, Yoshizo
- Subjects
- *
SENSORY ganglia , *GANGLIA , *CENTRAL nervous system , *SCIATIC nerve injuries , *SATELLITE cells , *NEUROGLIA - Abstract
• Infraorbital nerve constriction injury induced pain behavior. • Infraorbital nerve constriction injury induced satellite glial cell activation in trigeminal ganglia. • CXCL2 levels increased at day 1 of neuropathic pain induction and decreased gradually, with IL-10 levels showing the opposite trend. • Recombinant IL-10 or anti-CXCL2 injection into trigeminal ganglia decreased pain behavior. Many trigeminal neuropathic pain patients suffer severe chronic pain. The neuropathic pain might be related with cross-excitation of the neighboring neurons and satellite glial cells (SGCs) in the sensory ganglia and increasing the pain signals from the peripheral tissue to the central nervous system. We induced trigeminal neuropathic pain by infraorbital nerve constriction injury (IONC) in Sprague-Dawley rats. We tested cytokine (CXCL2 and IL-10) levels in trigeminal ganglia (TGs) after trigeminal neuropathic pain induction, and the effect of direct injection of the anti-CXCL2 and recombinant IL-10 into TG. We found that IONC induced pain behavior. Additionally, IONC induced satellite glial cell activation in TG and cytokine levels of TGs were changed after IONC. CXCL2 levels increased on day 1 of neuropathic pain induction and decreased gradually, with IL-10 levels showing the opposite trend. Recombinant IL-10 or anti-CXCL2 injection into TG decreased pain behavior. Our results show that IL-10 or anti-CXCL2 are therapy options for neuropathic pain. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
126. Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene.
- Author
-
Kujiraoka, Satoko, Tsunematsu, Takaaki, Sato, Yukiko, Yoshida, Maki, Ishikawa, Ayataka, Tohyama, Rei, Tanaka, Michio, Kobayashi, Yutaka, Kondo, Tomoyuki, Ushio, Aya, Otsuka, Kunihiro, Kurosawa, Mie, Saito, Masako, Yamada, Akiko, Arakaki, Rieko, Nagai, Hirokazu, Nikai, Hiromasa, Takeuchi, Kengo, Nagao, Toshitaka, and Miyamoto, Youji
- Subjects
- *
RENAL cell carcinoma , *ODONTOGENIC tumors , *MANDIBLE , *MICROARRAY technology , *GENE expression , *REVERSE transcriptase polymerase chain reaction , *CHIMERIC proteins , *TUMORS , *ANIMALS , *CANCER invasiveness , *CELL lines , *GENES , *MICE , *PROTEINS , *XENOGRAFTS - Abstract
Objective: Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumor (MOT) characterized by sheets and lobules of vacuolated and clear cells. To understand the biology of CCOC, we established a new cell line, CCOC-T, with EWSR1-ATF1 fusion gene from a mandible tumor with distant metastasis and characterized this cell line.Materials and Methods: To detect the EWSR1-ATF1 fusion gene, we used three CCOC cases, including the present case, by RT-PCR and FISH analysis. We characterized established CCOC-T cells by checking cell growth, invasion and the expression of odontogenic factors and bone-related factors. Moreover, the gene expression profile of CCOC-T cells was examined by microarray analysis.Results: Histologically, the primary tumor was comprised of cords and nests containing clear and squamoid cells separated by fibrous septa. In addition, ameloblastomatous islands with palisaded peripheral cells were observed, indicating probable odontogenic origin. This tumor expressed the fusion gene EWSR1-ATF1, which underlies the etiology of hyalinizing clear cell carcinoma (HCCC) and potentially that of CCOC. We found a breakpoint in the EWSR1-ATF1 fusion to be the same as that reported in HCCC. Established CCOC-T cells grew extremely slowly, but the cells showed highly invasive activity. Moreover, CCOC-T cells expressed bone-related molecules, odontogenic factors, and epithelial mesenchymal transition (EMT)-related molecules.Conclusion: To the best of our knowledge, this is the first report on the establishment of a CCOC cell line. CCOC-T cells serve as a useful in vitro model for understanding the pathogenesis and nature of MOT. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
127. Study of the pharmacokinetics of eriodictyol-6-C-β-d-glucoside, a flavonoid of rooibos (Aspalathus linearis) extract, after its oral administration in mice.
- Author
-
Yuyama, Kanako, Nakamura, Yoshitaka, Tateyama, Riho, Arakaki, Rieko, Tsutsui, Takuya, and Ishimaru, Naozumi
- Subjects
- *
FLAVONOID glycosides , *ROOIBOS tea , *SWEAT glands , *LACRIMAL apparatus , *EXOCRINE glands , *PHARMACOKINETICS - Abstract
• We developed a sample pretreatment procedure and E6CG analysis method using LC–MS/MS. • E6CG was quickly absorbed and its concentration peaked at 19.3 min after administration. • E6CG was distributed in the submandibular, sublingual, parotid, and lacrimal glands. • It was also distributed in the palm skin, including the sweat glands. Systemic dry syndrome affects quality of life, and various effective methods are being developed for its treatment. We recently found that rooibos (Aspalathus linearis) extract activates muscarinic M 3 receptor and improves dryness in mice and humans. We identified eriodictyol-6- C -β- D -glucoside (E6CG) as the active component affecting the secretory functions of exocrine glands; however, the pharmacokinetics and distribution of E6CG in exocrine glands have not been elucidated in mice receiving rooibos extract. We have developed a quantification method using LC–MS/MS to detect E6CG without an internal standard. Experiments on C57BL/6 mice administered rooibos extract showed that E6CG was transferred into blood plasma, with its concentration levels peaking 19.3 min after treatment. Substantial levels of E6CG were detected in the submandibular, sublingual, parotid, and lacrimal glands and in the sweat glands in palm skin. This study reports that rooibos extracts containing E6CG can be used as functional foods for improving systemic dryness. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
128. CD4 + T-cell-dependent differentiation of CD23 + follicular B cells contributes to the pulmonary pathology in a primary Sjögren's syndrome mouse model.
- Author
-
Sato-Fukuba M, Arakaki R, Ushio A, Otsuka K, Nagao R, Matsuzawa S, Tawara H, Tsunematsu T, and Ishimaru N
- Subjects
- Mice, Animals, Salivary Glands, B-Lymphocytes, Cell Differentiation, CD4-Positive T-Lymphocytes pathology, Sjogren's Syndrome
- Abstract
Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that affects the function of exocrine glands, such as the lacrimal and the salivary glands. Extraglandular lesions and malignant lymphoma also occur during the progressive stage of pSS. We have, herein, focused on the pulmonary lesions of pSS and have aimed clarifying their pathophysiological mechanism by comparing the glandular with the extraglandular lesions observed in a mouse model of pSS., Results: The histopathological analysis of lung tissues obtained from NFS/ sld mice that have undergone neonatal thymectomy was performed. Moreover, in vivo and in vitro experiments were conducted along with immunological analyses in order to characterize the unique phenotypes of the pulmonary lesions identified in these pSS model mice. Inflammatory lesions with a bronchus-associated lymphoid tissue-like structure were identified in the lungs of pSS model mice. In addition, relative to salivary gland lesions, pulmonary lesions showed increased CD23
+ follicular B (FB) cells. In vitro and pulmonary B cells were more readily driven to CD23+ FB cell phenotype than salivary gland B cells in pSS model mice. Furthermore, the CD23+ FB cell differentiation was found to be enhanced in a CD4+ T-cell-dependent manner under a Th2-type condition in the lungs of herein examined pSS model mice., Discussion: A Th2-type response in the pSS lung may promote the progression of autoimmune lesions through an enhanced abnormal differentiation of B cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sato-Fukuba, Arakaki, Ushio, Otsuka, Nagao, Matsuzawa, Tawara, Tsunematsu and Ishimaru.)- Published
- 2023
- Full Text
- View/download PDF
129. Cancer cell-derived novel periostin isoform promotes invasion in head and neck squamous cell carcinoma.
- Author
-
Wenhua S, Tsunematsu T, Umeda M, Tawara H, Fujiwara N, Mouri Y, Arakaki R, Ishimaru N, and Kudo Y
- Subjects
- Humans, Cell Line, Tumor, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Protein Isoforms genetics, Squamous Cell Carcinoma of Head and Neck genetics, Head and Neck Neoplasms genetics, Cell Adhesion Molecules metabolism
- Abstract
It recently has been reported that partial-epithelial-mesenchymal transition (p-EMT) program is associated with metastasis in head and neck squamous cell carcinoma (HNSCC). We previously have identified POSTN (which encodes periostin) as an invasion-promoting molecule in HNSCC. Interestingly, POSTN expression is frequently observed in cancer cells with higher p-EMT score by using a previous single-cell transcriptomic data of HNSCC cases. Although it is known that POSTN has 11 splicing variants, the role of them has not been determined in HNSCC. Here, we found that HNSCC cells with EMT features expressed POSTN isoforms, Iso3 (lacking exon 17 and 21) and Iso5 (lacking exon 17), whereas fibroblast expressed Iso3 and Iso4 (lacking exon 17, 18, and 21). The expression of POSTN Iso3 and Iso4 are known to be widely observed in various cell types including stromal cells. Therefore, we focused on the role of novel cancer cell-derived POSTN isoform, Iso5, in HNSCC. Single overexpression of POSTN Iso5 as well as Iso3 promoted invasion. Surprisingly, Iso5 synergistically promoted invasion together with Iso3. Notably, Iso5 as well as Iso3 upregulated p-EMT-related genes. We suggest that a novel cancer-specific POSTN isoform lacking exon 17 (Iso5) can be a useful marker for detecting cancer cells undergoing p-EMT. Moreover, a POSTN Iso5 can be a novel target for diagnosis and therapy in HNSCC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
130. Exposure to Multiwall Carbon Nanotubes Promotes Fibrous Proliferation by Production of Matrix Metalloproteinase-12 via NF-κB Activation in Chronic Peritonitis.
- Author
-
Tsunematsu T, Arakaki R, Sato M, Saito M, Otsuka K, Furukawa Y, Taquahashi Y, Kanno J, and Ishimaru N
- Abstract
The toxicologic effects of nanomaterials, such as carbon nanotubes (CNTs), on the immune system are understood well. However, the precise relationship between long-term exposure to CNTs and chronic inflammation remains unclear. In this study, a mouse model of chronic peritonitis was established using i.p. injection of multiwalled CNTs treated by the Taquann method with high dispersion efficiency. Chronic peritonitis with fibrosis was observed in Taquann-treated multiwalled CNT (T-CNT)-injected mice, but not in Taquann-treated titanium dioxide-injected mice. In vivo and in vitro experiments showed that matrix metalloproteinase-12 (MMP-12) of macrophages was up-regulated by T-CNT to enhance fibroblast activation and profibrotic molecule expression in fibroblasts. In addition, T-CNT-induced peritonitis reduced MMP-12 expression in Nfκb1
-/- mice, suggesting that MMP-12-producing macrophages play a key role in chronic inflammation due to T-CNT exposure through NF-κB activation. The results of this study could be helpful in understanding the molecular toxicity of nanomaterial and chronic inflammation., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
131. Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren's syndrome.
- Author
-
Sato M, Arakaki R, Tawara H, Nagao R, Tanaka H, Tamura K, Kawahito Y, Otsuka K, Ushio A, Tsunematsu T, and Ishimaru N
- Abstract
Objective: Innate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS., Methods: Multiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared by in vitro experiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice., Results: The number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice., Conclusion: The results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sato, Arakaki, Tawara, Nagao, Tanaka, Tamura, Kawahito, Otsuka, Ushio, Tsunematsu and Ishimaru.)
- Published
- 2022
- Full Text
- View/download PDF
132. PD-1 agonism by anti-CD80 inhibits T cell activation and alleviates autoimmunity.
- Author
-
Sugiura D, Okazaki IM, Maeda TK, Maruhashi T, Shimizu K, Arakaki R, Takemoto T, Ishimaru N, and Okazaki T
- Subjects
- Animals, Autoimmunity, B7-1 Antigen, B7-H1 Antigen metabolism, Mice, Programmed Cell Death 1 Receptor metabolism, T-Lymphocytes, Autoimmune Diseases, Neoplasms
- Abstract
Targeted blockade of the checkpoint molecule programmed cell death 1 (PD-1) can activate tumor-specific T cells to destroy tumors, whereas targeted potentiation of PD-1 is expected to suppress autoreactive T cells and alleviate autoimmune diseases. However, the development of methods to potentiate PD-1 remains challenging. Here we succeeded in eliciting PD-1 function by targeting the cis-PD-L1-CD80 duplex, formed by binding of CD80 to the PD-1 ligand PD-L1, that attenuates PD-L1-PD-1 binding and abrogates PD-1 function. By generating anti-CD80 antibodies that detach CD80 from the cis-PD-L1-CD80 duplex and enable PD-L1 to engage PD-1 in the presence of CD80, we demonstrate that the targeted dissociation of cis-PD-L1-CD80 duplex elicits PD-1 function in the condition where PD-1 function is otherwise restricted. We demonstrate using murine models that the removal of PD-1 restriction is effective in alleviating autoimmune disease symptoms. Our findings establish a method to potentiate PD-1 function and propose the removal of restraining mechanisms as an efficient strategy to potentiate the function of inhibitory molecules., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
- Full Text
- View/download PDF
133. Achaete-Scute Homologue 2-Regulated Follicular Helper T Cells Promote Autoimmunity in a Murine Model for Sjögren Syndrome.
- Author
-
Otsuka K, Yamada A, Saito M, Ushio A, Sato M, Kisoda S, Shao W, Tsunematsu T, Kudo Y, Arakaki R, and Ishimaru N
- Subjects
- Animals, Autoantibodies immunology, Autoantibodies metabolism, B-Lymphocytes metabolism, B-Lymphocytes pathology, Basic Helix-Loop-Helix Transcription Factors genetics, Cell Differentiation, Cytokines immunology, Cytokines metabolism, Female, Germinal Center metabolism, Germinal Center pathology, Mice, Mice, Inbred C57BL, Proto-Oncogene Proteins c-bcl-6 genetics, Proto-Oncogene Proteins c-bcl-6 metabolism, Sjogren's Syndrome metabolism, Sjogren's Syndrome pathology, T-Lymphocytes, Helper-Inducer metabolism, T-Lymphocytes, Helper-Inducer pathology, Autoimmunity immunology, B-Lymphocytes immunology, Basic Helix-Loop-Helix Transcription Factors metabolism, Disease Models, Animal, Germinal Center immunology, Sjogren's Syndrome immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Follicular helper T (Tfh) cells contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Herein, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model for Sjögren syndrome (SS) wherein the mice underwent neonatal thymectomy. Germinal center (GC) development was promoted in this SS model along with an increase of Tfh cells and GC B cells. The severity of the autoimmune lesions was correlated with the number of Tfh cells detected in the spleen of the SS model mice. In addition, treatment with an anti-CD20 monoclonal antibody effectively suppressed the autoimmune lesions with a reduction of Tfh cells and GC B cells. Comprehensive gene analysis revealed that several genes associated with Tfh cell differentiation, including achaete-scute homologue 2 (Ascl2), were up-regulated in peripheral CD25
- CD4+ T cells in SS model mice compared with those in control mice. Moreover, an experiment using CD4Cre Bcl6fl/fl mice that received neonatal thymectomy treatment demonstrated that Ascl2 contributes to the Tfh cell differentiation associated with autoimmunity during the early stages, independent of Bcl6. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
134. Novel effects of rooibos extract on tear and saliva secretion mediated by the muscarinic acetylcholine receptor 3 in mice.
- Author
-
Arakaki R, Ushio A, Kisoda S, Sato M, Nakamura Y, Yuyama K, Tateyama R, Morishita S, Monoi N, Kudo Y, and Ishimaru N
- Subjects
- Animals, Humans, Mice, Mice, Inbred C57BL, Plant Extracts, Quality of Life, Receptors, Muscarinic, Saliva, South Africa, Aspalathus
- Abstract
Objectives: Sicca syndrome is characterized by dry mouth and eyes and results in a reduction of the patient's quality of life. Various natural plants, including certain herbs, have long been employed to alleviate such symptoms. Rooibos grown in South Africa is one of the potent herbal plants used for the treating dry mouth. However, the precise mechanism of action by which rooibos alleviates symptoms of dryness remains unclear., Methods: The in vivo effects of rooibos extract (RE), which comprises eriodictyol-6-C-glucoside, on the secretory function of saliva and tears were analyzed after intraoral RE administration using wild-type C57BL/6 (B6) mice. In addition, the mechanisms of RE were investigated after administration of a muscarinic acetylcholine receptor 3 (M3R) antagonist., Results: Tear and saliva volumes in mice increased significantly and in a dose-dependent manner following intraoral RE administration compared to those in mice in the control group administered H
2 O. An experiment performed using darifenacin administration revealed that the effects of RE on secretory function were exerted via M3R., Conclusion: These results suggest that RE administration is an effective treatment for symptoms of dryness and may be used in clinical settings against sicca syndrome., (Copyright © 2019. Published by Elsevier B.V.)- Published
- 2019
- Full Text
- View/download PDF
135. NF-κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjögren's Syndrome.
- Author
-
Kurosawa M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Sprent J, and Ishimaru N
- Subjects
- Animals, Chemokine CXCL12 immunology, Chemotaxis, Leukocyte immunology, Disease Models, Animal, Gene Expression Regulation, In Vitro Techniques, Mice, Mice, Knockout, Receptors, CXCR4 immunology, Sjogren's Syndrome immunology, Transcription Factor RelB genetics, Chemotaxis, Leukocyte genetics, NF-kappa B p52 Subunit genetics, Receptors, CXCR4 genetics, Sjogren's Syndrome genetics, T-Lymphocytes immunology
- Abstract
Objective: Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T cell infiltration into target tissues, but the specific chemokines, receptors, and T cell populations remain largely unidentified. The aim of this study was to examine the role of the potent chemokine CXCL12 and its receptor CXCR4 in the T cell autoimmune response, using alymphoplasia (aly)/aly mice, a model of Sjögren's syndrome (SS)., Methods: T cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunologic analysis. An in vitro migration assay was used to assess T cell migratory activity toward several chemokines. Gene expression of chemokine receptors and transforming growth factor β receptors (TGFβRs) was measured by quantitative reverse transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was administered to the aly/aly mice in order to evaluate its suppressive effect on autoimmune lesions., Results: Effector memory T (TEM) cells derived from aly/aly mice demonstrated higher in vitro migratory activity toward CXCL12 than did TEM cells from aly/+ mice. CXCL12 expression was specifically up-regulated in the SS target cells of aly/aly mice. TEM cells from RelB
-/- mice, but not Nfkb1-/- mice, also showed high migratory activity toward CXCL12, implicating a role of the nonclassical RelB/NF-κB2 pathway in the regulation of TEM cell migration. TEM cells from aly/aly mice also overexpressed TGFβR type I (TGFβRI) and TGFβRII. The CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by reducing TEM cell infiltration., Conclusion: Our results suggest that the RelB/NF-κB2 pathway regulates T cell migration to autoimmune targets through TGFβ/TGFβR-dependent regulation of CXCL12/CXCR4 signaling. This suggests that these signaling pathways are potential therapeutic targets for the treatment of autoimmune diseases., (© 2017, American College of Rheumatology.)- Published
- 2017
- Full Text
- View/download PDF
136. Preventive effects of mouthguard use while sleeping on recurrent aphthous stomatitis: Preliminary interventional study.
- Author
-
Tada H, Fujiwara N, Tsunematsu T, Tada Y, Arakaki R, Tamaki N, Ishimaru N, and Kudo Y
- Abstract
Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulceration in the oral mucosa of otherwise healthy individuals and is often accompanied by severe pain. However, the etiology of RAS is not completely understood, and currently, no therapy can completely prevent RAS recurrence. In our clinical experience, we noticed that patients using a night guard, which is often used for bruxism treatment, did not develop RAS. Therefore, the aim of this study was to determine whether mouthguard use can suppress RAS development. The cohort of this interventional, prospective, single-center, and self-controlled study included 20 subjects who developed RAS at least once a month. The oral health of all the subjects was recorded for 60 days before and after intervention with a mouthguard. The average number of RAS incidences decreased from 5.5 to 1.0, the average days until healing decreased from 7.3 to 5.6, and the period with RAS decreased from 31.5 to 5.0 with mouthguard use. Mouthguard use may be beneficial for preventing RAS development.
- Published
- 2017
- Full Text
- View/download PDF
137. Human odontogenic epithelial cells derived from epithelial rests of Malassez possess stem cell properties.
- Author
-
Tsunematsu T, Fujiwara N, Yoshida M, Takayama Y, Kujiraoka S, Qi G, Kitagawa M, Kondo T, Yamada A, Arakaki R, Miyauchi M, Ogawa I, Abiko Y, Nikawa H, Murakami S, Takata T, Ishimaru N, and Kudo Y
- Subjects
- Adult Stem Cells, Cell Differentiation, Cell Separation, Cells, Cultured, Epithelial Cells, Gene Expression Profiling, Humans, Odontogenesis, Periodontal Ligament cytology
- Abstract
Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of the Hertwig's epithelial root sheath (HERS) that are involved in the formation of tooth roots. ERM cells are unique epithelial cells that remain in periodontal tissues throughout adult life. They have a functional role in the repair/regeneration of cement or enamel. Here, we isolated odontogenic epithelial cells from ERM in the periodontal ligament, and the cells were spontaneously immortalized. Immortalized odontogenic epithelial (iOdE) cells had the ability to form spheroids and expressed stem cell-related genes. Interestingly, iOdE cells underwent osteogenic differentiation, as demonstrated by the mineralization activity in vitro in mineralization-inducing media and formation of calcification foci in iOdE cells transplanted into immunocompromised mice. These findings suggest that a cell population with features similar to stem cells exists in ERM and that this cell population has a differentiation capacity for producing calcifications in a particular microenvironment. In summary, iOdE cells will provide a convenient cell source for tissue engineering and experimental models to investigate tooth growth, differentiation, and tumorigenesis.
- Published
- 2016
- Full Text
- View/download PDF
138. Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease.
- Author
-
Kondo T, Tsunematsu T, Yamada A, Arakaki R, Saito M, Otsuka K, Kujiraoka S, Ushio A, Kurosawa M, Kudo Y, and Ishimaru N
- Subjects
- Animals, Autoimmune Diseases genetics, Autoimmune Diseases immunology, Autoimmune Diseases metabolism, Cell Line, Tumor, Disease Models, Animal, Gene Expression drug effects, Gene Expression immunology, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit immunology, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Immunohistochemistry, Interferon-gamma genetics, Interferon-gamma immunology, Interferon-gamma metabolism, Macrophage Colony-Stimulating Factor genetics, Macrophage Colony-Stimulating Factor immunology, Macrophage Colony-Stimulating Factor pharmacology, Macrophages classification, Melanoma, Experimental blood supply, Melanoma, Experimental genetics, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Neovascularization, Pathologic genetics, Neovascularization, Pathologic metabolism, Reverse Transcriptase Polymerase Chain Reaction, Tumor Burden genetics, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A immunology, Vascular Endothelial Growth Factor A metabolism, Macrophages immunology, Melanoma, Experimental immunology, Neovascularization, Pathologic immunology, Tumor Burden immunology
- Abstract
Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor- overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co-culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1α in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth.
- Published
- 2016
- Full Text
- View/download PDF
139. Impaired expansion of regulatory T cells in a neonatal thymectomy-induced autoimmune mouse model.
- Author
-
Yamada A, Ushio A, Arakaki R, Tsunematsu T, Kudo Y, Hayashi Y, and Ishimaru N
- Subjects
- Animals, Animals, Newborn, Autoimmunity, Cytokines immunology, Cytokines metabolism, Disease Models, Animal, Female, Interferon-gamma metabolism, Mice, Mice, Inbred C57BL, Mutation, Receptor, Transforming Growth Factor-beta Type I, Specific Pathogen-Free Organisms, Thymectomy adverse effects, Transforming Growth Factor beta metabolism, Cell Differentiation, Interferon-gamma immunology, Protein Serine-Threonine Kinases immunology, Receptors, Transforming Growth Factor beta immunology, T-Lymphocytes, Regulatory immunology, Transforming Growth Factor beta immunology
- Abstract
Neonatal thymectomy in certain mouse strains is known to induce organ-specific autoimmunity due to impaired functions of T cells, including Foxp3(+) regulatory T (Treg) cells in the thymus. The precise mechanism underlying the induction of autoimmunity by neonatal thymectomy remains unclear. One possibility is that depletion of Treg cells breaks down peripheral tolerance. We examined the functions of Treg cells by using a murine Sjögren syndrome model of NFS/sld mice that underwent neonatal thymectomy. The ratio of Treg cells to effector memory phenotype T cells in thymectomy mice was significantly lower than that of nonthymectomy mice. In addition, in vitro induction of peripherally induced Treg cells by transforming growth factor-β (TGF-β) using naive T cells from Sjögren syndrome model mice was severely impaired. The mRNA expression of TGF-β receptor I and II and Smad3 and -4 in the TGF-β-induced signal transduction pathway of Treg cells in this Sjögren syndrome model were lower than those of control mice. In addition, Treg cells in this Sjögren syndrome model exhibited an interferon-γ-producing Th1-like phenotype that resembled effector T cells. In conclusion, these results suggest that abnormal expansion and differentiation of Treg cells and inflammatory cytokines produced by Treg cells contribute to the development of autoimmunity., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
140. Aromatase controls Sjögren syndrome-like lesions through monocyte chemotactic protein-1 in target organ and adipose tissue-associated macrophages.
- Author
-
Iwasa A, Arakaki R, Honma N, Ushio A, Yamada A, Kondo T, Kurosawa E, Kujiraoka S, Tsunematsu T, Kudo Y, Tanaka E, Yoshimura N, Harada N, Hayashi Y, and Ishimaru N
- Subjects
- Animals, Aromatase genetics, Aromatase Inhibitors chemistry, Autoimmunity, Chemokine CCL2 genetics, DNA-Binding Proteins genetics, Female, Macrophages cytology, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, RNA, Messenger metabolism, Salivary Glands metabolism, Sjogren's Syndrome genetics, Adipose Tissue, White cytology, Aromatase metabolism, Chemokine CCL2 metabolism, Macrophages metabolism, Sjogren's Syndrome enzymology
- Abstract
Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is an enzyme that converts androgens to estrogens. Herein, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 increased in white adipose tissue of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M1 macrophages was observed in white adipose tissue of ArKO mice. A significantly increased monocyte chemotactic protein-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjögren syndrome were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play a key role in the pathogenesis of Sjögren syndrome-like lesions by controlling the target organ and adipose tissue-associated macrophage., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
141. [II. Autoimmune disease: 5. Sjögren's syndrome].
- Author
-
Hayashi Y, Arakaki R, and Ishimaru N
- Subjects
- Female, Humans, Sjogren's Syndrome complications, Kidney Diseases etiology, Sjogren's Syndrome immunology
- Published
- 2011
- Full Text
- View/download PDF
142. [A case of sensory ataxic neuropathy and polymyositis of perivascular type associated with Sjögren's syndrome].
- Author
-
Taguchi T, Matsubara S, Miyamoto K, Mizutani T, Hayashi H, Arakaki R, and Hayashi Y
- Subjects
- Ataxia pathology, Female, Ganglia, Spinal pathology, Humans, Middle Aged, Peripheral Nervous System Diseases pathology, Polymyositis pathology, Sensation Disorders pathology, Ataxia complications, Peripheral Nervous System Diseases complications, Polymyositis complications, Sensation Disorders complications, Sjogren's Syndrome complications
- Abstract
A 53-year old woman was admitted with of sensory disturbance and weakness of lower limbs which had progressed slowly in the previous ten years. A diagnosis of sensory ataxic neuropathy associated with Sjögren's syndrome was made. A sural nerve biopsy showed marked loss of myelinated fibers. A muscle biopsy revealed atrophy of muscle fibers along with perivascular cellular infiltration. The dorsal root ganglia have been considered to be the main site affected in the ataxic neuropathy in Sjögren's syndrome. However, the evidence for that was meager. The perivascular inflammatory change observed in the muscle may also have existed in the peripheral nervous system including the dorsal root ganglia.
- Published
- 2004
143. Estrogen deficiency accelerates murine autoimmune arthritis associated with receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenesis.
- Author
-
Yoneda T, Ishimaru N, Arakaki R, Kobayashi M, Izawa T, Moriyama K, and Hayashi Y
- Subjects
- Animals, Arthritis pathology, Arthritis physiopathology, Arthritis, Rheumatoid, Bone Resorption, Carrier Proteins genetics, Cytokines genetics, Disease Models, Animal, Estrogens physiology, Female, Gene Expression, Glycoproteins genetics, Joints pathology, Matrix Metalloproteinase 3 genetics, Matrix Metalloproteinase 9 genetics, Membrane Glycoproteins genetics, Mice, Osteoprotegerin, Ovariectomy, RANK Ligand, RNA, Messenger analysis, Receptor Activator of Nuclear Factor-kappa B, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Tumor Necrosis Factor, Reverse Transcriptase Polymerase Chain Reaction, Arthritis immunology, Autoimmune Diseases physiopathology, Carrier Proteins physiology, Estrogens deficiency, Membrane Glycoproteins physiology, Osteoclasts physiology
- Abstract
The aims of this study were to evaluate the in vivo effects of estrogen deficiency in MRL/lpr mice as a model for rheumatoid arthritis and to analyze the possible relationship between immune dysregulation and receptor activator of nuclear factor-kappaB ligand (RANKL)-mediated osteoclastogenesis. Experimental studies were performed in ovariectomized (Ovx)-MRL/lpr, Ovx-MRL+/+, sham-operated-MRL/lpr, and sham-operated-MRL+/+ mice. Severe autoimmune arthritis developed in younger Ovx-MRL/lpr mice until 24 wk of age, whereas these lesions were entirely recovered by pharmacological levels of estrogen administration. A significant elevation in serum rheumatoid factor, anti-double-stranded DNA, and anti-type II collagen was found in Ovx-MRL/lpr mice and recovered in mice that underwent estrogen administration. A high proportion of CD4(+) T cells bearing RANKL was found, and an enhanced expression of RANKL mRNA and an impaired osteoprotegerin mRNA was detected in the synovium. An increase in both osteoclast formation and bone resorption pits was found. These results indicate that estrogen deficiency may play a crucial role in acceleration of autoimmune arthritis associated with RANKL-mediated osteoclastogenesis in a murine model for rheumatoid arthritis.
- Published
- 2004
- Full Text
- View/download PDF
144. Anti-alpha-fodrin autoantibodies in Moyamoya disease.
- Author
-
Ogawa K, Nagahiro S, Arakaki R, Ishimaru N, Kobayashi M, and Hayashi Y
- Subjects
- Adolescent, Adult, Aged, Apoptosis immunology, Autoantibodies pharmacology, Carrier Proteins genetics, Cells, Cultured, Child, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Endothelium, Vascular immunology, Female, Flow Cytometry, Humans, Immunoglobulin G blood, Immunoglobulin G pharmacology, Male, Microfilament Proteins genetics, Middle Aged, Moyamoya Disease blood, Recombinant Proteins genetics, Recombinant Proteins immunology, Tumor Necrosis Factor-alpha pharmacology, Autoantibodies blood, Carrier Proteins immunology, Microfilament Proteins immunology, Moyamoya Disease immunology
- Abstract
Background and Purpose: Moyamoya disease (MMD) is a rare entity that results in progressive occlusion of the arteries of the circle of Willis, but the pathogenesis of MMD is unknown., Methods: MMD sera (n=32) were tested for anti-endothelial cell antibodies by enzyme-linked immunoassays and flow cytometric analysis. Apoptosis was induced in human umbilical vein endothelial cells by tumor necrosis factor-alpha., Results: We found that a high proportion of MMD sera had anti-endothelial cell antibodies with apoptotic stimuli. Prominent reactivities of MMD sera (72%) with recombinant human alpha-fodrin were observed., Conclusions: Our study demonstrates that MMD sera contain a high incidence of anti-alpha-fodrin autoantibodies, providing new insight into the mechanisms of occlusion of MMD arteries.
- Published
- 2003
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.