LY294002 inhibits TLR3/4‐mediated IFN‐β production via inhibition of IRF3 activation with a PI3K‐independent mechanism
Copyright policy )LY294002 inhibits TLR3/4‐mediated IFN‐β production via inhibition of IRF3 activation with a PI3K‐independent mechanism
TLR3 and TLR4 utilize adaptor TRIF to activate interferon regulatory factor 3 (IRF3), resulting in interferon β (IFN‐β) production to mediate anti‐viral infection. In this report, we analyzed the effect of two known phosphatidylinositol 3‐kinase (PI3K) inhibitors LY294002 and wortmannin on LPS‐ and poly(I:C)‐induced IFN‐β production in peritoneal macrophages. LY294002 inhibited LPS‐ and poly(I:C)‐induced IFN‐β transcription and secretion. In contrast, wortmannin could not inhibit IFN‐β production. Furthermore, IRF3 transcriptional activation and binding to IFN‐β promoter were found to be inhibited by LY294002. Therefore, our findings demonstrate LY294002 negatively regulates LPS‐ and poly(I:C)‐induced IFN‐β production through inhibition of IRF3 activation in a PI3K‐independent manner.
- Shandong Women’s University China (People's Republic of)
Lipopolysaccharides, Morpholines, Mice, Phosphatidylinositol 3-Kinases, Toll-like receptor, Animals, Humans, Enzyme Inhibitors, Promoter Regions, Genetic, IFN-β, Phosphoinositide-3 Kinase Inhibitors, Interferon-beta, IRF3, Toll-Like Receptor 3, Androstadienes, Mice, Inbred C57BL, Toll-Like Receptor 4, HEK293 Cells, Poly I-C, Chromones, Macrophages, Peritoneal, LY294002, Interferon Regulatory Factor-3, Wortmannin, Phosphatidylinositol 3-kinase
Lipopolysaccharides, Morpholines, Mice, Phosphatidylinositol 3-Kinases, Toll-like receptor, Animals, Humans, Enzyme Inhibitors, Promoter Regions, Genetic, IFN-β, Phosphoinositide-3 Kinase Inhibitors, Interferon-beta, IRF3, Toll-Like Receptor 3, Androstadienes, Mice, Inbred C57BL, Toll-Like Receptor 4, HEK293 Cells, Poly I-C, Chromones, Macrophages, Peritoneal, LY294002, Interferon Regulatory Factor-3, Wortmannin, Phosphatidylinositol 3-kinase
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