The effect of PPARalpha and PPARgamma ligands on inflammation and ABCA1 expression in cultured gallbladder epithelial cells.
The preservation of gallbladder function by control of inflammation and elimination of cholesterol accumulation in gallbladder epithelial 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 PPARalpha and PPARgamma 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. PPARalpha and PPARgamma expression was observed and increased in GBEC treated with WY-14643 (PPARalpha ligand), troglitazone (PPARgamma ligand), and lipopolysaccharide (LPS) compared to the no-treatment control and PPARalpha( 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 TNFalpha mRNA expression was suppressed by pretreatment with WY-14643 and troglitazone preceding LPS treatment in GBEC. PPAR ligands, especially PPARgamma, 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.
Lee
Jin
J
Division of Gastroenterology, Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, 94-200, Youngdungpo-Dong, Youngdungpo-Gu, Seoul 150-030, South Korea. jinlee@medimail.co.kr
Hong
Eun Mi
EM
Byun
Hyun Woo
HW
Choi
Min Ho
MH
Jang
Hyun Joo
HJ
Eun
Chang Soo
CS
Kae
Sea Hyub
SH
Choi
Ho Soon
HS
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005704:Gallbladder / Q000166:cytology* / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008024:Ligands; D047493:PPAR alpha / Q000494:pharmacology*; D047495:PPAR gamma / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008024:Ligands; D047493:PPAR alpha; D047495:PPAR gamma