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Publication : LY294002 inhibits TLR3/4-mediated IFN-β production via inhibition of IRF3 activation with a PI3K-independent mechanism.

First Author  Zhao W Year  2012
Journal  FEBS Lett Volume  586
Issue  6 Pages  705-10
PubMed ID  22285490 Mgi Jnum  J:181915
Mgi Id  MGI:5314430 Doi  10.1016/j.febslet.2012.01.016
Citation  Zhao W, et al. (2012) LY294002 inhibits TLR3/4-mediated IFN-beta production via inhibition of IRF3 activation with a PI3K-independent mechanism. FEBS Lett 586(6):705-10
abstractText  TLR3 and TLR4 utilize adaptor TRIF to activate interferon regulatory factor 3 (IRF3), resulting in interferon beta (IFN-beta) 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-beta production in peritoneal macrophages. LY294002 inhibited LPS- and poly(I:C)-induced IFN-beta transcription and secretion. In contrast, wortmannin could not inhibit IFN-beta production. Furthermore, IRF3 transcriptional activation and binding to IFN-beta promoter were found to be inhibited by LY294002. Therefore, our findings demonstrate LY294002 negatively regulates LPS- and poly(I:C)-induced IFN-beta production through inhibition of IRF3 activation in a PI3K-independent manner.
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