456 OSTEOPONTIN, A PUTATIVE MARKER FOR DUCTULAR REACTION, IS INDUCED BY JAK/STAT3 ACTIVATION IN HUMAN BILIARY EPITHELIAL CELLS

S173activate PPARa and PPARg in various cells, but there are no studies in GBEC.The aim of this study was to know the effect of statins on PPAR and ABCA1 expression in cultured, and to demonstrate anti-inflammatory effect of statins in GBEC.Methods: Canine GBEC were cultured on Petri-dish coated with collagen matrix.The protein expression of PPARa, PPARg and ABCA1 was measured by Western blotting following treatment of pravastatin (15 mM), NO-pravastatin (15 mM), simvastatin (15 m), PPARa ligand (WY-14643, 100 mM), PPARg ligand (troglitazone 10 mM) to the culture media of the indicated cells.The mRNA expression of ABCA1 and LXRa, compared to positive (22-R-hydroxycholesterol, 10 mM), was estimated by RT-PCR, In order to demonstrate the preventive effect of statins on inflammation, mRNA of TNFa, compared to positive control (lipopolysaccharide, 100 mg/mL), was measured by RT-PCR after 24 hours pre-treatment of pravastatin, NO-pravastatin and simvastatin preceding 1 hour lipopolysaccharide loading.Results: Pravastatin, NO-pravastatin, and simvastatin increased protein expression of PPARa, PPARg and ABCA1, and mRNA expression of ABCA1 and LXRa in GBEC.Pre-treatment of Pravastatin, NO-pravastatin and simvastatin repressed the production of TNFa mRNA induced by lipopolysaccharide.Conclusions: Statins can contribute to preserve GB function through PPARa and PPARg activation which have anti-inflammatory effect by suppression of pro-inflammatory cytokine, and ABCA1 activation mediated by LXRa which prevent accumulation of cholesterol in GBEC.