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- Title
A role for IRF3-dependent RXRalpha repression in hepatotoxicity associated with viral infections.
- Authors
Chow, Edward K; Castrillo, Antonio; Shahangian, Arash; Pei, Liming; O'Connell, Ryan M; Modlin, Robert L; Tontonoz, Peter; Cheng, Genhong
- Abstract
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 (RXRalpha) 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 RXRalpha as a molecular mechanism for pathogen-associated metabolic diseases.
- Publication
The Journal of experimental medicine, 2006, Vol 203, Issue 12, p2589
- ISSN
0022-1007
- Publication type
Journal Article
- DOI
10.1084/jem.20060929