LY294002 inhibits TLR3/4-mediated IFN-尾 production via inhibition of IRF3 activation with a PI3K-independent mechanism

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• 作者：Wei Zhaop>1p> ; Jianni Qip>1p> ; Lijuan Wang ; Meng Zhang ; Peng Wang ; Chengjiang Gaop> ; p>p>cgao@sdu.edu.cnp>
• 关键词：PI3K ; phosphatidylinositol 3-kinase ; TLR ; toll-like receptor ; IRF3 ; interferon regulatory factor 3 ; IFN-尾 ; interferon 尾
• 刊名：FEBS Letters
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：23 March, 2012
• 卷：586
• 期：6
• 页码：705-710
• 文件大小：637 K

摘要

TLR3 and TLR4 utilize adaptor TRIF to activate interferon regulatory factor 3 (IRF3), resulting in interferon 尾 (IFN-尾) 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-尾 production in peritoneal macrophages. LY294002 inhibited LPS- and poly(I:C)-induced IFN-尾 transcription and secretion. In contrast, wortmannin could not inhibit IFN-尾 production. Furthermore, IRF3 transcriptional activation and binding to IFN-尾 promoter were found to be inhibited by LY294002. Therefore, our findings demonstrate LY294002 negatively regulates LPS- and poly(I:C)-induced IFN-尾 production through inhibition of IRF3 activation in a PI3K-independent manner.