2001 Fiscal Year Final Research Report Summary
Analysis of Toll-like receptors in LPS signaling
| Project/Area Number |
12670297
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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 |
Immunology
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| Research Institution | Nagoya University |
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Principal Investigator |
MATSUGUCHI Tetsuya Graduate School of Medicine Nagoya University Assistant Professor, 大学院・医学研究科, 助教授 (10303629)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Toll-like receptor / macrophage / NF-KB / JNK / LPS / phosphatase / MKP / innate immunity |
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| Research Abstract |
[Instroduction] Toll-like receptors (TLRs) are a family of proteins recognizing molecular patterns of pathogens and induce downstream signals including NF-kB and MAP kinases. Among TLRs TLR2 and 4 are especially important in host defense by recognizing bacterial cell wall components. However, the exact mechanisms of their expressional regulation have not been clearly shown. Although MyD88 plays an important role in their downstream signals, LPS can still activate both NF-kB and MAP kinase activation in MyD88-KO mice indicating the involvement of other signaling molecules.
[Results/Discussion] 1) We compared gene expression of TLR2 and TLR4 in mouse macrophages and found that TLR2, but not TLR4, is induced by LPS and proinflamtnatory cytokines. We then cloned the promoter region of mouse TLR2 gene and identified two NF-kB binding sites playing essential roles in the TLR2 indcuction.2) Utilizing Yeast two hybrid screening, we identified JIP3 (JNK interacting protein 3) as a TLR4-binding protein. JIP3 overexpression enhanced LPSmediated JNK activation in macrophages indicating it is involved in the TLR4 downstream signaling.3) We newly identified a novel MAP kinase phosphatase named MKP-M (MAP kinase phosphatase isolated from macrophages). MKP-M specifically dephosphorylated JNK and is an important regulator of JNK activity in LPS-stimulated macrophages.
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Research Products
(34 results)
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[Publications] Iwami, K., Matsguchi, T., Masuda, A., Kikuchi, T., Musikacharoen, T., and Yoshikai, Y.: "Naturally Occurring Soluble Form of Mouse Toll-Like Receptor 4 Inhibits"J. Immunol. 165. 6682-6686 (2000)
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[Publications] Mokuno, Y., Matsuguchi, T., Takano, M., Nishimura, H., Washizu, J., Ogawa, T., Takeuchi, O., Akira, S., Nimura, Y., Yoshikai Y.: "Expression of Toll-like Receptor 2 on γδ8 T cells bearing invariant Vγ6/Vδ1 induced by Escherichia coli infection in mice"J. Immunol.. 165. 931-940 (2000)
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[Publications] Kikuchi, T., Matsuguchi. T., Tsuboi, N., Mitani, A., Tanaka, S., Matsuoka, M.,Yamamoto, G., Hishikawa, T., Noguchi, T., Yoshikai, Y.: "Gene Expression of Osteoclast Differentiation Factor is induced by Lipopolysaccharide in Mouse Osteoblasts via Toll-like Receptors"J. Immunol. 166. 3574-3579 (2001)
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