The serine protease inhibitor antithrombin III inhibits LPS‐mediated NF‐κB activation by TLR‐4

FEBS Letters

O'Neill, Luke A.J²  Worrall, D.Margaret¹  Mansell, Ashley²  Reinicke, Anna² 

[1] Department of Biochemistry, University College Dublin, Belfield, Dublin 4, Ireland;Department of Biochemistry and Biotechnology Institute, Trinity College Dublin, Dublin 2, Ireland

关键词: Lipopolysaccharide;    Inflammation;    Signal transduction;    Monocyte;    Transcription factor;    TLR;    Toll-like receptor;    ATIII;    antithrombin III;    L-ATIII;    latent antithrombin III;    LPS;    lipopolysaccharide;    EMSA;    electrophoretic mobility shift assay;    IL-1;    interleukin-1;    TNF;    tumour necrosis factor;   

DOI  :  10.1016/S0014-5793(01)03077-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In Drosophila, the Toll family of proteins mediates the innate immune response. Toll is activated by Spaetzle, which is generated in response to pathogens via a serine protease cascade. We wished to investigate if lipopolysaccharides (LPS) might activate Toll-like receptor (TLR) 4 via a serine protease in humans. The serpin antithrombin III (ATIII) and the thrombin inhibitor hirudin both inhibited nuclear factor (NF)-κB activation by LPS and Lipid A. ATIII and hirudin were also able to inhibit LPS-induced NF-κB activation in cells stably transfected with TLR4. These results suggest that LPS may activate a mammalian serine protease, which generates a product required for TLR4 signalling.

【 授权许可】

Unknown