The serine protease inhibitor antithrombin III inhibits LPS‐mediated NF‐κB activation by TLR‐4
Open Access
- 23 November 2001
- journal article
- Published by Wiley in FEBS Letters
- Vol. 508 (3), 313-317
- https://doi.org/10.1016/s0014-5793(01)03077-0
Abstract
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.Keywords
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