Effect of peroxisome proliferator-activated receptor-γ ligands on the expression of retinoic acid-inducible gene-I in endothelial cells stimulated with lipopolysaccharide

Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH box protein family and designated as a putative RNA helicase. RIG-I is implicated in host defense and inflammatory reactions by regulating the expression of various genes. RIG-I is expressed in endothelial cells and upregulated with lipopolysaccharide (LPS). Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor and regulates gene expressions in response to its specific ligands. In the present study, we examined the effect of PPAR-gamma ligands on the LPS-induced RIG-I expression in cultured human umbilical vein endothelial cells (HUVEC). 15-Deoxy-Delta(12.14)-prostaglandin J(2) (15d-PGJ(2)), a metabolite of PGD(2), is a natural ligand for PPAR-gamma and known to modulate inflammatory reactions by regulating the expression of various genes in PPAR-gamma-dependent and -independent manners. LPS-induced RIG-I expression in HUVEC was inhibited by pretreatment of the cells with 15d-PGJ(2) in time-and concentration-dependent manners. However, ciglitazone and bisphenol A diglycide ether, authentic and specific ligands for PPAR-gamma, did not affect the RIG-I expression. These results suggest that 15d-PGJ(2) inhibits LPS-induced RIG-I expression through a mechanism independent on PPAR-gamma. 15d-PGJ(2), may regulate inflammatory reactions, at least in part, by inhibiting the expression of RIG-I. (c) 2005 Elsevier Inc. All rights reserved.