Regulation of macrophage immune response by HGF-beta/mannose receptor axis.
| Project/Area Number |
26860046
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | Kinjo Gakuin University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | HGF-β / HGF / Mannose receptor / IL-10 / IL-4 / STAT3 / 肝細胞増殖因子 / マンノース受容体 / M2マクロファージ |
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| Outline of Final Research Achievements |
Production of hepatocyte growth factor (HGF) is induced by tissue damage, while, in the tissues with inflammation or damage, HGF is degraded by proteases from inflammatory cells such as neutrophils. Digestion of HGF by proteases yields HGF β-chain remnant (HGF-β) that binds to mannose receptor (MR) expressed on macrophages. Herein, we showed that HGF-β induces IL-10 production by macrophages, which is dependent on the presence of IL-4. HGF-β promoted IL-4-mediated activation of JAK proteins and downstream STAT3 tyrosine phosphorylation. In addition, HGF-β increased STAT3 serine phosphorylation and its nuclear translocation through p44/p42 MAPK pathway. Enhancement of IL-4-mediated STAT3 activation by HGF-β was required for the induction of IL-10 production by Mφ. These findings raise the possibility that HGF-β generated through fragmentation of HGF in damaged tissues induces IL-10-producing Mφ with immunoregulatory phenotype.
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Report
(3 results)
Research Products
(6 results)
