| Project/Area Number |
20790354
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Osaka University |
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Principal Investigator |
ABE Takayuki Osaka University, 微生物病研究所, 助教 (90403203)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 病原性 / HCV / TLR / CD44 / IP-10 |
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| Research Abstract |
Although infiltration of lymphocytes and natural killer cells was observed in the liver of acute and chronic hepatitis C patients, the mechanisms of the liver injury during hepatitis C virus (HCV) infection are not well understood. Interferon-gamma-inducible protein 10 (IP-10), that selectively recruits activated T cells to the sites of inflammation, has shown to be expressed in the livers of the chronic hepatitis C patients. We have shown previously that IP-10 production was significantly enhanced in HCV RNA replicon cells and the human hepatoma cell lines infected with HCV through a TLR2-dependent signaling pathway. By the DNA microarray analysis, we have identified CD44 as a one of the candidates involved in the inflammatory response through a TLR signaling pathway. CD44 is a broadly distributed type I transmembrane glycoprotein and a receptor for glycosaminoglycan hyaluronan (HA). HA also works as a ligand for TLR2 and serum HA levels in the chronic hepatitis C patients were shown to increase according to the progression of liver fibrosis. IP-10 production was also induced by the treatment with HA in the replicon cells, but not in the naive cells. These results suggest that the IP-10 production in the HCV replicon cells is regulated by HA stimulation through the engagement of TLR2 and CD44, and that serum HA in chronic hepatitis C patients participates in the induction of IP-10.
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