徳島大学 教育・研究者情報データベース(EDB)

1. (英) Ohnishi Koji

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2. (英) Komohara Yoshihiro

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3. (英) Fujiwara Yukio

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4. (英) Takemura Kenichi

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5. (英) Lei XiaoFeng

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6. (英) Nakagawa Takenobu

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7. 坂下 直実

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8. (英) Takeya Motohiro

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(英) Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204).

(英) The class A scavenger receptor (SR-A, CD204), one of the principal receptors expressed on macrophages, has been found to regulate inflammatory response and attenuate septic endotoxemia. However, the detailed mechanism of this process has not yet been well characterized. To clarify the regulative mechanisms of lipopolysaccharide (LPS)-induced macrophage activation by SR-A, we evaluated the activation of Toll-like receptor 4 (TLR4)-mediated signaling molecules in SR-A-deficient (SR-A(-/-)) macrophages. In a septic shock model, the blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and interferon (IFN)-β were significantly increased in SR-A(-/-) mice compared to wild-type mice, and elevated nuclear factor kappa B (NFκB) activation was detected in SR-A(-/-) macrophages. SR-A deletion increased the production of pro-inflammatory cytokines, and the phosphorylation of mitogen-activated protein kinase (MAPK) and NFκB in vitro. SR-A deletion also promoted the nuclear translocation of NFκB and IFN regulatory factor (IRF)-3. In addition, a competitive binding assay with acetylated low-density lipoprotein, an SR-A-specific ligand, and anti-SR-A antibody induced significant activation of TLR4-mediated signaling molecules in wild-type macrophages but not in SR-A(-/-) macrophages. These results suggest that SR-A suppresses the macrophage activation by inhibiting the binding of LPS to TLR4 in a competitive manner and it plays a pivotal role in the regulation of the LPS-induced inflammatory response.

1. (英) Animals
2. (英) Cell Nucleus
3. 細胞質分裂(cytokinesis)
4. 炎症(inflammation)
5. (英) Interferon Regulatory Factor-3
6. (英) Lipopolysaccharides
7. (英) Macrophage Activation
8. (英) Macrophages
9. 男性(male)
10. (英) Mice
11. (英) Mice, Inbred C57BL
12. (英) NF-kappa B
13. (英) Scavenger Receptors, Class A
14. (英) Sequence Deletion
15. (英) Shock, Septic
16. (英) Toll-Like Receptor 4

1. (英) Article.Affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't