PT  - JOURNAL ARTICLE
AU  - Gang Hu
AU  - Chenshu Xu
AU  - Jeff L. Staudinger
TI  - Pregnane X Receptor Is SUMOylated to Repress the Inflammatory Response
AID  - 10.1124/jpet.110.171744
DP  - 2010 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 342--350
VI  - 335
IP  - 2
4099  - http://jpet.aspetjournals.org/content/335/2/342.short
4100  - http://jpet.aspetjournals.org/content/335/2/342.full
SO  - J Pharmacol Exp Ther2010 Nov 01; 335
AB  - Long-term treatment of patients with the macrolide antibiotic and prototypical activator of pregnane X receptor (PXR) rifampicin (Rif) inhibits the inflammatory response in liver. We show here that activation of the inflammatory response in hepatocytes strongly modulates SUMOylation of ligand-bound PXR. We provide evidence that the SUMOylated PXR contains SUMO3 chains, and feedback represses the immune response in hepatocytes. This information represents the first step in developing novel pharmaceutical strategies to treat inflammatory liver disease and prevent adverse drug reactions in patients experiencing acute or systemic inflammation. These studies also provide a molecular rationale for constructing a novel paradigm that uniquely defines the molecular basis of the interface between PXR-mediated gene activation, drug metabolism, and inflammation.