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

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• 作者：Mansell ; Ashley ; Reinicke ; Anna ; et. al.
• 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 ; interleuk
• 刊名：FEBS Letters
• 出版年：2001
• 出版时间：November 23, 2001
• 年：2001
• 卷：508
• 期：3
• 页码：313-317
• 全文大小：213 K

文摘

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.