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An essential role for IFN-β in the induction of IFN-stimulated gene expression by LPS in macrophages.

Abstract：

:TLR agonists such as LPS and poly(I:C) induce expression of type I IFNs, such as IFN-α and -β, by macrophages. To examine the role of IFN-β in the induction of ISGs by LPS, we compared the ability of LPS to induce ISGF3 activity and ISG expression in bone marrow-derived macrophages from WT and Ifnb1(-/-) mice. We found that LPS treatment activated ISGF3 and induced expression of ISGs such as Oas1, Mx1, Ddx58 (RIG-I), and Ifih1 (MDA5) in WT macrophages, but not in macrophages derived from Ifnb1(-/-) mice or Ifnar1(-/-) mice. The inability of LPS to induce activation of ISGF3 and ISG expression in Ifnb1(-/-) macrophages correlated with the failure of LPS to induce activation of STAT1 and -2 in these cells. Consistent with these findings, LPS treatment also failed to induce ISG expression in bone marrow-derived macrophages from Stat2 KO mice. Although activation of ISGF3 and induction of ISG expression by LPS was abrogated in Ifnb1(-/-) and Ifnar1(-/-) macrophages, activation of NF-κB and induction of NF-κB-responsive genes, such as Tnf (TNF-α) and Il1b (IL-1β), were not affected by deletion of either the IFN-β or IFN-αR1 genes. These findings demonstrate that induction of ISGF3 activity and ISG expression by LPS is critically dependent on intermediate production of IFN-β and autocrine signaling through type I IFN receptors.

journal_name

J Leukoc Biol

journal_title

Journal of leukocyte biology

authors

Sheikh F,Dickensheets H,Gamero AM,Vogel SN,Donnelly RP

doi

10.1189/jlb.2A0414-191R

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

591-600

issue

4

eissn

0741-5400

issn

1938-3673

pii

jlb.2A0414-191R

journal_volume

96

pub_type

杂志文章

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