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. |