| Project/Area Number |
18590715
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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 | Yamagata University |
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Principal Investigator |
LI Shao Yamagata University, Dept. of Public Health, Assistant Professor (80344787)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Takahumi Yamagata University, Dept. of Gastroenterology, Assistant Professor (80250918)
KAWATA Sumio Yamagata University, Dept. of Gastroenterology, Professor (90183285)
FUKAO Akira Yamagata University, Dept. of Public Health, Professor (80156736)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Hepatitis C / Innate immune / TLR2 / Single nucleotide polymorphism / HCV replicon |
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| Research Abstract |
The progression of liver fibrosis in chronic hepatitis C is influenced by both genetic and environmental factors although its detailed mechanism has not been unraveled yet. Inflammation and activation of hepatic stellate cell are thought to be the principal effectors of hepatic fibrogenesis. Recent studies suggested that toll-like receptor 2 (TLR2), an innate immune sensor, plays an important role in the inflammation response triggered by HCV core and NS3 proteins. To investigate whether functional polymorphisms across the TLR2-related genes affect the liver fibrosis progression, a genetic association study was conducted in patients with chronic hepatitis C. The results showed that a deletion polymorphism in TLR2 gene is significantly associated with liver fibrosis progression. We hypothesized that this variant in TLR2 gene affects the liver fibrosis by altering the expression of inflammation cytokines or influencing the HCV replication in hepatocytes. To test the hypothesis, we transfected TLR2-siRNA into HCV replicon cell lines Huh7.5 that stably produce infectious virions. Silencing of TLR2 expression had no significant effect on HCV replication. We further assessed the difference in inflammatory cytokine expression in monocytes between individuals with deletion-type and wild-type TLR2. Monocytes from the deletion-type-TLR2-individuals produced more IL-6 in response to stimulation with HCV. This finding supported the possibility that the polymorphism in TLR2 affects the cytokine expression and activity, consequently influencing the liver fibrosis progression in chronic hepatitis C.
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