A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections

被引：32

作者：

Chow, Edward K.

Castrillo, Antonio

Shahangian, Arash

Pei, Liming

O'Connell, Ryan M.

Modlin, Robert L.

Tontonoz, Peter

Cheng, Genhong ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Howard Hughes Med Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, David Geffen Sch Med, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Div Dermatol, David Geffen Sch Med, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Med Scientist Training Program, David Geffen Sch Med, Los Angeles, CA 90095 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2006年 / 203卷 / 12期

关键词：

D O I：

10.1084/jem.20060929

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Viral infections and antiviral responses have been linked to several metabolic diseases, including Reye's syndrome, which is aspirin-induced hepatotoxicity in the context of a viral infection. We identify an interferon regulatory factor 3 (IRF3)-dependent but type I interferon-independent pathway that strongly inhibits the expression of retinoid X receptor alpha (RXR alpha) and suppresses the induction of its downstream target genes, including those involved in hepatic detoxification. Activation of IRF3 by viral infection in vivo greatly enhances bile acid- and aspirin-induced hepatotoxicity. Our results provide a critical link between the innate immune response and host metabolism, identifying IRF3-mediated down-regulation of RXR alpha as a molecular mechanism for pathogen-associated metabolic diseases.

引用

页码：2589 / 2602

页数：14

共 75 条

[1] Recruitment of IκBα to the hes1 promoter is associated with transcriptional repression [J].