ライ ショウホウ   RAI Shouho
  雷 小峰
   所属   埼玉医科大学  医学部 国際医療センター 皮膚科(皮膚腫瘍科)
   職種   助教
論文種別 学術雑誌(原著)
言語種別 英語
査読の有無 査読あり
表題 Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204)
掲載誌名 正式名:BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSNコード:0006-291X
出版社 ACADEMIC PRESS INC ELSEVIER SCIENCE
巻・号・頁 411(3),516-522頁
著者・共著者 Koji Ohnishi,Yoshihiro Komohara,Yukio Fujiwara,Kenichi Takemura,XiaoFeng Lei,Takenobu Nakagawa,Naomi Sakashita,Motohiro Takeya
発行年月 2011/08
概要 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 (TNE)-alpha, interleukin (IL)-6 and interferon (IFN)-beta were significantly increased in SR-A(-/-) mice compared to wild-type mice, and elevated nuclear factor kappa B (NF kappa B) 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 NF kappa B in vitro. SR-A deletion also promoted the nuclear translocation of NF kappa B 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. (C) 2011 Elsevier Inc. All rights reserved.
DOI 10.1016/j.bbrc.2011.06.161
PMID 21756882