1998 Fiscal Year Final Research Report Summary
MOCECULAR MECHANISMS OF HEPATOCYTOTOXICITY IN AUTOIMMUNE LIVER DISEASES
| Project/Area Number |
09670576
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | The JIKEI University School of Medicine |
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Principal Investigator |
ZENIYA Mikio The JIKEI University School of Medicine Faculty of Medicine Associate Professor, 医学部, 助教授 (70138767)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hiroki The JIKEI University School of Medicine Faculty of Medicine Fellow, 医学部, 助手 (80256403)
WATANABE Fumitoki The JIKEI University School of Medicine Faculty of Medicine Fellow, 医学部, 助手 (90231711)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Autoimmune Hepatitis / Th1 / Th2 balance / TCR reperatoire / Vbeta7 / 肝内サイトカイン発現 |
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| Research Abstract |
In order to clarify the molecular mechanisms of hepatotoxicity in autoimmune liver disease, we analysed the cytokine balance of autoimmune hepatitis (AIH) and primary billiary cirrhosis (PBC) by using newly developed intrecellular cytokine detection technique. The level of Th1 cytokine such as IFN-gamma in the active phase of AIH was high and IFN-gamma seemed to participate in the pathogenesis of active phase of AIH.Interestingly, it became clear that the level of IFN-gamma decreased during steroid therapy. On the contrary, the level of IL-10 increased during steroid therapy. These results indicated that Th1 dominancy was one of the particular charactor of AIH.
We also analysed the TCR reperatoire of liver infiltrating lymphocyte (LIL) in AIH before and after steroid therapy to clarify the unique TCR V beta subfamily which may participate in the pathogenesis of AIH at active phase. Although there was no particular TCR V beta subfamily which was commonly used by LIL in AIH at active phase, unique amino acid was detected at N-D-N resion of CDR3 resion of V beta 7 which was shared by LIL of two HLA A24-DR4 positive patients. Interestingly, V beta 7 subfamily was disapeared from LIL after steroid therapy. These results indicated the possibility that unique amino acid which was detected at N-D-N resion of CDR3 resion of V beta 7 recognize the disease specific autoantigen of AIH.
For father study, we should make clear that whether LIL-T cell which use such unique V beta subfamily particpate in the pathogenesis of AIH by recognizing the autoantigen and by secreting Th1 cytokine such as IFN-gamma.
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Research Products
(9 results)
