The effect of PPAR alpha and PPAR gamma ligands on inflammation and ABCA1 expression in cultured gallbladder epithelial cells

Abstract

The preservation of gallbladder function by control of inflammation and elimination of cholesterol accumulation in gallbladder epithelia] cells (GBEC) could contribute to the prevention of gallstone formation and cholecystitis. Peroxisome proliferator-activated receptors (PPARs) modulate inflammation and lipid metabolism in various cells and GBEC efflux of excessive amounts of absorbed cholesterol through the ATP-binding cassette transporter A1 (ABCA1)-mediated pathway. The aim of this study was to determine whether ligands of PPAR alpha and PPAR modulate inflammation and have an effect on ABCA1 expression in GBEC. Canine GBEC were cultured on dishes coated with collagen matrix. We performed Western blot analysis for the expression of specific protein and/or RT-PCR for the expression of specific mRNA. PPAR alpha and PPAR gamma expression was observed and increased in GBEC treated with WY-14643 (PPAR alpha ligand), troglitazone (PPAR gamma ligand), and lipopolysaccharide (LPS) compared to the no-treatment control and PPAR alpha antagonist (GW-9662) treatment group. WY-14643, troglitazone, and LPS also induced an increase in the expression of ABCA1 protein and mRNA in cultured GBEC. LPS-induced TNF alpha mRNA expression was suppressed by pre-treatment with WY-14643 and troglitazone preceding LPS treatment in GBEC. PPAR ligands, especially PPAR gamma, may preserve gallbladder function by suppression of inflammatory reaction and prevention of cholesterol accumulation in GBEC, contributing to the prevention of gallstone formation and progression to cholecystitis.