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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Zhao W,Qi J,Wang L,Zhang M,Wang P,Gao C

doi

10.1016/j.febslet.2012.01.016

subject

Has Abstract

pub_date

2012-03-23 00:00:00

pages

705-10

issue

6

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(12)00036-1

journal_volume

586

pub_type

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