10 results on '"Shiho Morimoto"'
Search Results
2. Correction: Critical Role of an Antiviral Stress Granule Containing RIG-I and PKR in Viral Detection and Innate Immunity.
- Author
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Koji Onomoto, Michihiko Jogi, Ji-Seung Yoo, Ryo Narita, Shiho Morimoto, Azumi Takemura, Suryaprakash Sambhara, Atushi Kawaguchi, Suguru Osari, Kyosuke Nagata, Tomoh Matsumiya, Hideo Namiki, Mitsutoshi Yoneyama, and Takashi Fujita
- Subjects
Medicine ,Science - Published
- 2012
- Full Text
- View/download PDF
3. Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity.
- Author
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Koji Onomoto, Michihiko Jogi, Ji-Seung Yoo, Ryo Narita, Shiho Morimoto, Azumi Takemura, Suryaprakash Sambhara, Atushi Kawaguchi, Suguru Osari, Kyosuke Nagata, Tomoh Matsumiya, Hideo Namiki, Mitsutoshi Yoneyama, and Takashi Fujita
- Subjects
Medicine ,Science - Abstract
Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) function as cytoplasmic sensors for viral RNA to initiate antiviral responses including type I interferon (IFN) production. It has been unclear how RIG-I encounters and senses viral RNA. To address this issue, we examined intracellular localization of RIG-I in response to viral infection using newly generated anti-RIG-I antibody. Immunohistochemical analysis revealed that RLRs localized in virus-induced granules containing stress granule (SG) markers together with viral RNA and antiviral proteins. Because of similarity in morphology and components, we termed these aggregates antiviral stress granules (avSGs). Influenza A virus (IAV) deficient in non-structural protein 1 (NS1) efficiently generated avSGs as well as IFN, however IAV encoding NS1 produced little. Inhibition of avSGs formation by removal of either the SG component or double-stranded RNA (dsRNA)-dependent protein kinase (PKR) resulted in diminished IFN production and concomitant enhancement of viral replication. Furthermore, we observed that transfection of dsRNA resulted in IFN production in an avSGs-dependent manner. These results strongly suggest that the avSG is the locus for non-self RNA sensing and the orchestration of multiple proteins is critical in the triggering of antiviral responses.
- Published
- 2012
- Full Text
- View/download PDF
4. Dysregulation of IFN system can lead to poor response to pegylated interferon and ribavirin therapy in chronic hepatitis C.
- Author
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Koji Onomoto, Shiho Morimoto, Takahisa Kawaguchi, Hidenori Toyoda, Masami Tanaka, Masahiko Kuroda, Kazuko Uno, Takashi Kumada, Fumihiko Matsuda, Kunitada Shimotohno, Takashi Fujita, and Yoshiki Murakami
- Subjects
Medicine ,Science - Abstract
BACKGROUND:Despite being expensive, the standard combination of pegylated interferon (Peg-IFN)-α and ribavirin used to treat chronic hepatitis C (CH) results in a moderate clearance rate and a plethora of side effects. This makes it necessary to predict patient outcome so as to improve the accuracy of treatment. Although the antiviral mechanism of genetically altered IL28B is unknown, IL28B polymorphism is considered a good predictor of IFN combination treatment outcome. METHODOLOGY:Using microarray, we quantified the expression profile of 237 IFN related genes in 87 CH liver biopsy specimens to clarify the relationship between IFN pathway and viral elimination, and to predict patients' clinical outcome. In 72 out of 87 patients we also analyzed IL28B polymorphism (rs8099917). PRINCIPAL FINDINGS:Five IFN related-genes (IFI27, IFI 44, ISG15, MX1, and OAS1) had expression levels significantly higher in nonresponders (NR) than in normal liver (NL) and sustained virological responders (SVR); this high expression was also frequently seen in cases with the minor (TG or GG) IL28B genotype. The expression pattern of 31 IFN related-genes also differed significantly between NR and NL. We predicted drug response in NR with 86.1% accuracy by diagonal linear discriminant analysis (DLDA). CONCLUSION:IFN system dysregulation before treatment was associated with poor IFN therapy response. Determining IFN related-gene expression pattern based on patients' response to combination therapy, allowed us to predict drug response with high accuracy. This method can be applied to establishing novel antiviral therapies and strategies for patients using a more individual approach.
- Published
- 2011
- Full Text
- View/download PDF
5. Iron uptake mediated by the plant-derived chelator nicotianamine in the small intestine
- Author
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Shiho Morimoto, Yoshiko Murata, Masami Yoshida, Takehiro Watanabe, Kosuke Namba, and Naho Sakamoto
- Subjects
Male ,0301 basic medicine ,5-HTP, 5-hydroxytryptophan ,Xenopus ,Phytochemicals ,Caco-2 cells ,FMOC, 9-fluorenylmethyloxycarbonyl ,Biochemistry ,Mice ,Xenopus laevis ,chemistry.chemical_compound ,DMT1, divalent metal transporter ,Intestine, Small ,Nicotianamine ,Cells, Cultured ,Chelating Agents ,Mice, Inbred ICR ,SLC36A1 ,biology ,Chemistry ,plant-derived chelator ,NA, nicotianamine ,transport metal ,Jejunum ,medicine.anatomical_structure ,transporter ,Azetidinecarboxylic Acid ,Research Article ,Duodenum ,Iron ,Biological Availability ,MAs, phytosiderophores ,Dcytb, duodenal cytochrome b ,PEPT1, oligopeptide transporter ,03 medical and health sciences ,Duodenal cytochrome B ,medicine ,Animals ,Humans ,Amino acid transporter ,oocyte ,intestine ,Molecular Biology ,TLC, thin layer chromatography ,030102 biochemistry & molecular biology ,PAT1, proton-coupled amino acid transporter ,nicotianamine ,Biological Transport ,Cell Biology ,DMT1 ,Small intestine ,Bioavailability ,FPN1, ferroportin1 ,030104 developmental biology ,Intestinal Absorption ,biology.protein ,YS1/YSL, yellow stripe 1/yellow stripe like - Abstract
Iron is an essential metal for all living organisms that is absorbed in the intestinal cells as a heme-chelated or free form. It is unclear how important plant-derived chelators, such as nicotianamine (NA), an organic small molecule that is ubiquitous in crops, vegetables, and various other foods, contribute to iron bioavailability in mammals. We performed electrophysiological assays with Xenopus laevis oocytes and radioactive tracer experiments with Caco-2 cells. The findings revealed that the proton-coupled amino acid transporter SLC36A1 (PAT1) transports iron in the form of NA-Fe (II) complex in vitro. Decreased expression of hPAT1 by RNA interference in Caco-2 cells reduced the uptake of NA-59Fe (II) complex. The uptake of inorganic 59Fe (II) was relatively unaffected. These results imply that PAT1 transports iron as a NA-Fe (II) complex. The rate of 59Fe absorption in the spleen, liver, and kidney was higher when mice were orally administered NA-59Fe (II) compared with free 59Fe (II). The profile of site-specific PAT1 expression in the mouse intestine coincided with those of NA and iron contents, which were the highest in the proximal jejunum. Orally administered NA-59Fe (II) complex in mice was detected in the proximal jejunum by thin layer chromatography. In contrast, much less 59Fe (or NA) was detected in the duodenum, where the divalent metal transporter SLC11A2 (DMT1) absorbs free Fe (II). The collective results revealed the role of PAT1 in NA-Fe (II) absorption in the intestine and potential implication of NA in iron uptake in mammals.
- Published
- 2021
6. Generation and Characterization of Severe Combined Immunodeficiency Rats
- Author
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Jun-ichiro Yomoda, Jun Hirose, Junya Kobayashi, Asato Tachibana, Takashi Kuramoto, Kazuto Yoshimi, Ami Yanagi, Akiko Takizawa, Takeshi Watanabe, Koji Tanabe, Yayoi Kunihiro, Chise Tateno, Saeko Ishida, Shiho Morimoto, Tomoji Mashimo, Birger Voigt, Tadao Serikawa, Hiroshi Hiai, and Kenshi Komatsu
- Subjects
Pluripotent Stem Cells ,Xenotransplantation ,medicine.medical_treatment ,Lymphocyte ,Transplantation, Heterologous ,DNA-Activated Protein Kinase ,Mice, SCID ,Biology ,Rats, Mutant Strains ,General Biochemistry, Genetics and Molecular Biology ,Gene Knockout Techniques ,Mice ,medicine ,Animals ,Humans ,lcsh:QH301-705.5 ,Immunodeficiency ,Severe combined immunodeficiency ,PRKDC Gene ,medicine.disease ,Phenotype ,Rats ,Transplantation ,Disease Models, Animal ,medicine.anatomical_structure ,lcsh:Biology (General) ,Immunology ,Severe Combined Immunodeficiency ,Stem cell ,Interleukin Receptor Common gamma Subunit - Abstract
Severe combined immunodeficiency (SCID) mice, the most widely used animal model of DNA-PKcs (Prkdc) deficiency, have contributed enormously to our understanding of immunodeficiency, lymphocyte development, and DNA-repair mechanisms, and they are ideal hosts for allogeneic and xenogeneic tissue transplantation. Here, we use zinc-finger nucleases to generate rats that lack either the Prkdc gene (SCID) or the Prkdc and Il2rg genes (referred to as F344-scid gamma [FSG] rats). SCID rats show several phenotypic differences from SCID mice, including growth retardation, premature senescence, and a more severe immunodeficiency without "leaky" phenotypes. Double-knockout FSG rats show an even more immunocompromised phenotype, such as the abolishment of natural killer cells.Finally, xenotransplantation of human induced pluripotent stem cells, ovarian cancer cells, and hepatocytes shows that SCID and FSG rats can act as hosts for xenogeneic tissue grafts and stem cell transplantation and may be useful for preclinical testing of new drugs., 重症免疫不全SCIDラットの作製 : ヒトiPS細胞、がん細胞、肝細胞をラット体内で培養することに成功. 京都大学プレスリリース. 2012-09-14.
- Published
- 2012
- Full Text
- View/download PDF
7. Critical Role of an Antiviral Stress Granule Containing RIG-I and PKR in Viral Detection and Innate Immunity
- Author
-
Koji Onomoto, Michihiko Jogi, Ji-Seung Yoo, Ryo Narita, Shiho Morimoto, Azumi Takemura, Suryaprakash Sambhara, Atushi Kawaguchi, Suguru Osari, Kyosuke Nagata, Tomoh Matsumiya, Hideo Namiki, Mitsutoshi Yoneyama, and Takashi Fujita
- Subjects
Multidisciplinary ,Science ,lcsh:R ,lcsh:Medicine ,Medicine ,Correction ,lcsh:Q ,lcsh:Science - Published
- 2013
8. Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity
- Author
-
Suguru Osari, Michihiko Jogi, Kyosuke Nagata, Shiho Morimoto, Tomoh Matsumiya, Suryaprakash Sambhara, Ryo Narita, Koji Onomoto, Azumi Takemura, Takashi Fujita, Ji-Seung Yoo, Atushi Kawaguchi, Mitsutoshi Yoneyama, and Hideo Namiki
- Subjects
Viral Diseases ,viruses ,lcsh:Medicine ,Antibodies, Viral ,Biochemistry ,DEAD-box RNA Helicases ,Mice ,eIF-2 Kinase ,Interferon ,Chlorocebus aethiops ,Molecular Cell Biology ,lcsh:Science ,Immune Response ,Cellular Stress Responses ,Mice, Knockout ,Multidisciplinary ,RIG-I ,Immunohistochemistry ,Innate Immunity ,RNA silencing ,Infectious Diseases ,Influenza A virus ,Interferon Type I ,Cytochemistry ,DEAD Box Protein 58 ,RNA, Viral ,Medicine ,Immunohistochemical Analysis ,Immunocytochemistry ,Research Article ,medicine.drug ,Immunology ,Biology ,Cytoplasmic Granules ,Immune Activation ,Stress granule ,Orthomyxoviridae Infections ,medicine ,Animals ,Humans ,Immunoassays ,Vero Cells ,lcsh:R ,Immunity ,RNA ,Immune Defense ,Fibroblasts ,Virology ,Protein kinase R ,Immunity, Innate ,Influenza ,Viral replication ,Immunologic Techniques ,lcsh:Q ,HeLa Cells - Abstract
Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) function as cytoplasmic sensors for viral RNA to initiate antiviral responses including type I interferon (IFN) production. It has been unclear how RIG-I encounters and senses viral RNA. To address this issue, we examined intracellular localization of RIG-I in response to viral infection using newly generated anti-RIG-I antibody. Immunohistochemical analysis revealed that RLRs localized in virus-induced granules containing stress granule (SG) markers together with viral RNA and antiviral proteins. Because of similarity in morphology and components, we termed these aggregates antiviral stress granules (avSGs). Influenza A virus (IAV) deficient in non-structural protein 1 (NS1) efficiently generated avSGs as well as IFN, however IAV encoding NS1 produced little. Inhibition of avSGs formation by removal of either the SG component or double-stranded RNA (dsRNA)-dependent protein kinase (PKR) resulted in diminished IFN production and concomitant enhancement of viral replication. Furthermore, we observed that transfection of dsRNA resulted in IFN production in an avSGs-dependent manner. These results strongly suggest that the avSG is the locus for non-self RNA sensing and the orchestration of multiple proteins is critical in the triggering of antiviral responses.
- Published
- 2012
9. Virus-infection or 5'ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1
- Author
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Mitsutoshi Yoneyama, Shiho Morimoto, Koji Onomoto, Azumi Takemura, Takashi Fujita, Kazuhide Onoguchi, Hideo Namiki, Shiori Takamatsu, Michihiko Jogi, and Ilkka Julkunen
- Subjects
lcsh:Immunologic diseases. Allergy ,Immunology/Innate Immunity ,Immunology ,Mitochondrial Membrane Transport Proteins ,Microbiology ,Cell Line ,GTP Phosphohydrolases ,Mitochondrial Proteins ,Mice ,Mitochondrial membrane transport protein ,Interferon ,Virology ,Genetics ,medicine ,Animals ,Humans ,MFN1 ,lcsh:QH301-705.5 ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Innate immune system ,biology ,Membrane Transport Proteins ,RNA ,Transfection ,Immunity, Innate ,Mitochondria ,Cell biology ,lcsh:Biology (General) ,mitochondrial fusion ,biology.protein ,RNA, Viral ,Parasitology ,lcsh:RC581-607 ,Bacterial outer membrane ,Research Article ,medicine.drug - Abstract
In virus-infected cells, RIG-I-like receptor (RLR) recognizes cytoplasmic viral RNA and triggers innate immune responses including production of type I and III interferon (IFN) and the subsequent expression of IFN-inducible genes. Interferon-β promoter stimulator 1 (IPS-1, also known as MAVS, VISA and Cardif) is a downstream molecule of RLR and is expressed on the outer membrane of mitochondria. While it is known that the location of IPS-1 is essential to its function, its underlying mechanism is unknown. Our aim in this study was to delineate the function of mitochondria so as to identify more precisely its role in innate immunity. In doing so we discovered that viral infection as well as transfection with 5′ppp-RNA resulted in the redistribution of IPS-1 to form speckle-like aggregates in cells. We further found that Mitofusin 1 (MFN1), a key regulator of mitochondrial fusion and a protein associated with IPS-1 on the outer membrane of mitochondria, positively regulates RLR-mediated innate antiviral responses. Conversely, specific knockdown of MFN1 abrogates both the virus-induced redistribution of IPS-1 and IFN production. Our study suggests that mitochondria participate in the segregation of IPS-1 through their fusion processes., Author Summary Virus-infections, such as influenza and chronic hepatitis C, are prominent diseases and outbreaks of newly emerging viruses are serious problems for modern society. Higher animals, including humans, are genetically equipped with mechanisms, collectively known as innate immunity, to counteract viral infections. RIG-I-like receptor (RLR), a cytoplasmic sensor, contributes to immune regulation by detecting infections by RNA viruses and triggering a series of responses which results in the activation of innate antiviral genes. Furthermore, it has been demonstrated that IPS-1, the adaptor protein of RLR, is expressed on mitochondrial outer membrane. Mitochondrion is an organelle of prokaryotic cell origin; it regulates energy production, and is involved in cell growth and cell death. Why IPS-1 is located on the mitochondrial outer membrane and how mitochondria are involved in antiviral signaling are yet to be explained clearly. In this report, we discovered that mitochondrial fusion protein MFN1 plays a novel function to mediate IPS-1 redistribution, which appears to be a critical step in RLR signaling.
- Published
- 2010
10. Dysregulation of IFN System Can Lead to Poor Response to Pegylated Interferon and Ribavirin Therapy in Chronic Hepatitis C
- Author
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Shiho Morimoto, Takashi Kumada, Takashi Fujita, Koji Onomoto, Yoshiki Murakami, Fumihiko Matsuda, Masami Tanaka, Hidenori Toyoda, Kazuko Uno, Masahiko Kuroda, Takahisa Kawaguchi, and Kunitada Shimotohno
- Subjects
Male ,Microarrays ,Gastroenterology and hepatology ,Gene Expression ,lcsh:Medicine ,Genome-wide association study ,medicine.disease_cause ,Hepatitis ,Polyethylene Glycols ,chemistry.chemical_compound ,Pegylated interferon ,Treatment Failure ,Precision Medicine ,lcsh:Science ,Lead (electronics) ,Multidisciplinary ,Interleukin ,Genomics ,Middle Aged ,Prognosis ,Hepatitis C ,Recombinant Proteins ,Infectious hepatitis ,Treatment Outcome ,Medicine ,Infectious diseases ,Drug Therapy, Combination ,Female ,Research Article ,medicine.drug ,Drugs and Devices ,Drug Research and Development ,Hepatitis C virus ,Alpha interferon ,Viral diseases ,Interferon alpha-2 ,Biology ,Antiviral Agents ,Molecular Genetics ,Predictive Value of Tests ,Ribavirin ,Genetics ,medicine ,Humans ,Genetic Association Studies ,Liver diseases ,Aged ,Clinical Genetics ,Polymorphism, Genetic ,Gene Expression Profiling ,Interleukins ,lcsh:R ,Computational Biology ,Interferon-alpha ,Human Genetics ,Hepatitis C, Chronic ,Gene Expression Regulation ,chemistry ,Pharmacogenetics ,Immunology ,lcsh:Q ,Interferons ,Genome Expression Analysis - Abstract
Background Despite being expensive, the standard combination of pegylated interferon (Peg-IFN)- α and ribavirin used to treat chronic hepatitis C (CH) results in a moderate clearance rate and a plethora of side effects. This makes it necessary to predict patient outcome so as to improve the accuracy of treatment. Although the antiviral mechanism of genetically altered IL28B is unknown, IL28B polymorphism is considered a good predictor of IFN combination treatment outcome. Methodology Using microarray, we quantified the expression profile of 237 IFN related genes in 87 CH liver biopsy specimens to clarify the relationship between IFN pathway and viral elimination, and to predict patients' clinical outcome. In 72 out of 87 patients we also analyzed IL28B polymorphism (rs8099917). Principal Findings Five IFN related-genes (IFI27, IFI 44, ISG15, MX1, and OAS1) had expression levels significantly higher in nonresponders (NR) than in normal liver (NL) and sustained virological responders (SVR); this high expression was also frequently seen in cases with the minor (TG or GG) IL28B genotype. The expression pattern of 31 IFN related-genes also differed significantly between NR and NL. We predicted drug response in NR with 86.1% accuracy by diagonal linear discriminant analysis (DLDA). Conclusion IFN system dysregulation before treatment was associated with poor IFN therapy response. Determining IFN related-gene expression pattern based on patients' response to combination therapy, allowed us to predict drug response with high accuracy. This method can be applied to establishing novel antiviral therapies and strategies for patients using a more individual approach.
- Published
- 2011
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