2004 Fiscal Year Final Research Report Summary
ANALYSIS OF THE PATHOGENESIS OF PRIMARY BILIARY CIRRHOSIS BY USING ANIMAL MODEL THAT IS ESTABLISHED BY MULTI STEP BREAKING OF TOLERANCE
| Project/Area Number |
14570512
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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 | JIKEI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
ZENIYA Mikio JIKEI UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助教授 (70138767)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hiroki JIKEI UNIVERSITY SCHOOL OF MEDICINE, LECTURE, 医学部, 講師 (80256403)
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| Project Period (FY) |
2002 – 2004
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| Keywords | PBC / Animal Model / Dendritic cell / Regulatory cell |
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| Research Abstract |
Background : We tried to analyze the pathogenesis of primary biliary cirrhosis(PBC) by using animal model that was established by multi step breakdown of self-tolerance.
Methods and Results : <First year> : At first we tried to establish animal model of PBC by inoculating the dendritic cell that was pulsed with recombinant PDC-E2,but bile duct injury was not observed in that model. Next we tried to make the model by inoculating the fusion cell(FC) of dendritic cell and bile duct cell following injection of IL-12. The bile duct injury was observed in that model.
<Second year> : We analyzed the immunological condition of established model. The number of intrahepatic Tr cell which produce IL-10 and TGF-B was not changed after FC inoculation. The number of intrahepatic CD25 CD4 positive T reg was slightly decreased after FC inoculation, but the profile of cytokine production of T reg was not changed after FC inoculation. The degree of intrahepatic accumulation of activated T cell was increased after IL-12 inoculation. The degree of the expressions of ICAM-1,VCAM-1 and VAP-1 on sinusoidal endothelial cell was increased after IL-12 inoculation.
<Third year> : We tried to identify the auto-antigen in this animal model by using SELEX method, but we could not detect it because of technical problem of experiment.
Conclusion : These findings indicate that the decrease of intrahepatic regulatory cell participated in the pathogenesis of PBC.
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