A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections
Open Access
- 30 October 2006
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 203 (12), 2589-2602
- https://doi.org/10.1084/jem.20060929
Abstract
Viral infections and antiviral responses have been linked to several metabolic diseases, including Reye9s 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 α (RXRα) 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 RXRα as a molecular mechanism for pathogen-associated metabolic diseases.This publication has 76 references indexed in Scilit:
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