Realtime qPCR showed a significant induction of NLRP3 (p<0. 05), IL-1β (p<0. 05), INF۷（p<0. 05) and IL-10 (p<0. 05) in the WT mice. The induction of these genes was significantly reduced in the galectin 3 knockout mice (NLRP3, p<0. 01; IL-1β, p<0. 05). Co-IP assay showed that galectin 3 associated with the NLRP3 in HSC and KC. The DCA-induced NLRP3, IL-1β, INF۷ and IL-10 expression were abolished in the galectin 3 siRNA transfected HSC and KC. Conclusion:

Galectin3 is an important mediator of inflammasome INCB024360 clinical trial activation in active HSC and KC during cholestatic liver injury resulting in the release of proinflammatory mediators. Galectin 3 therefore could become a potential target for novel treatment see more approaches in cholestatic liver diseases. Disclosures: The following people have nothing to disclose: Xiaosong Jiang, Tzu-I Chao, FuTong Liu, M. Eric Gershwin, Natalie Torok Background: Pregnancy disturbs bile secretory function and can unmask cholestatic disease in genetically-predisposed individuals. The mechanisms underlying pregnancy-induced changes in bile secretion are unknown but a pro-cholestatic hepatic gene expression profile occurs during pregnancy in mice. Significantly reduced expression of hepatic import genes [i. e. Ntcp, organic

anion-transporting polypeptide] and export genes [i. e. Bsep, bile salt export pump and multidrug resistance-associated protein 2 (Mrp2)] as well as up-regulation of the bile salt biosynthesis enzymes Cyp7a1 and Cyp8b1 have been reported. Fibroblast growth factor (FGF)15 is an entero-hepatic hormone known regulate bile salt synthesis. Defective Fgf15 signaling could contribute to the biliary phenotype observed in pregnant mice. Aim: to evaluate the effect medchemexpress of pregnancy on ileal expression of FGF 15 in mice. Methods: 10 week-old C57BL6

female mice (n=6 per group) were divided in 3 experimental groups: control group (CG), pregnancy group (PG) and 2 weeks-fed cholestyramine 3% group (CTM, positive control). Serum and biliary parameters and epatic gene expression (RTPCR) of Cyp7a1, Ntcp, Bsep and Mrp2 as well as ileal expression of Fgf15 were analyzed. Results: Body/liver weight ratio was significantly higher in CG compared to PG (21. 49±0. 5 in CG, 16. 23±0. 3 in PG, p <0. 05). While aminotransferases and serum bile acids levels were similar in all groups, bile flow and biliary secretion of bile salts were significantly decreased in PG [bile flow (μL/minxgliver): 1. 6±0. 13 μL/minxgliver vs. 2. 3±0. 22 in CG, biliary bile salt secretion (nmoles/minxgliver): 187. 7±33. 6 vs. 87. 3±8. 32 in CG, p <0. 05]. This correlated with a significant decrease in hepatic expression of biliary transporters [Ntcp (−47%), Bsep (−44%) and Mrp2 (−39%)] in PG. Cyp7a1 hepatic expression was induced in PG (3. 6-fold) and CTM (7. 9-fold). This was associated to a reduced ileal Fgf15 gene expression in both groups (relative mRNA levels: 0. 38±0. 1 in PG and 0.