Regulation of cytochrome P450 4F11 expression by liver X receptor alpha.

ABSTRACT

Cytochrome P450 4F (CYP4F) enzymes are responsible for the metabolism of eicosanoids, which play important roles in inflammation. Nuclear receptor liver X receptor alpha (LXRα) is a critical signal node connecting inflammation and lipid metabolism. Studies revealed that the release of cytokines and nuclear factor-κB (NF-κB) can change the CYP4F11 expression in HepG2 cells. However, the effect of LXRα on the CYP4F family and the underlying mechanism remain unclear. This study found that CYP4F11 is a target gene of LXRα. Luciferase assays and siRNA transfection showed that LXRα increased the transcription of CYP4F11 and LXRα agonist GW3965 could induce the expression of CYP4F11 by activating the LXRα-CYP4F11 pathway. Besides, overexpression of CYP4F11 could decrease TNF-α and IL-1ß in lipopolysaccharide (LPS)-induced THP-1 cells. The finding of the regulation of CYP4F11 may contribute to the anti-inflammatory activity of LXRα agonists.