Ursodeoxycholate inhibits mast cell activation and reverses biliary injury and fibrosis in Mdr2^-/- mice and human primary sclerosing cholangitis.

ABSTRACT: Ursodeoxycholic acid (UDCA) is used to treat biliary disorders; and, bile acids alter mast cell (MC) histamine release. MCs infiltrate Mdr2^-/- mice liver (model of primary sclerosing cholangitis (PSC)). MC-derived histamine increases inflammation, hepatic stellate cell (HSC) activation and fibrosis. The objective was to determine the effects of UDCA treatment on MC infiltration, biliary damage, inflammation and fibrosis in Mdr2^-/- mice and human PSC. Wild-type and Mdr2^-/- mice were fed bile acid control diet or UDCA (0.5% wt/wt). Human samples were collected from control and PSC patients treated with placebo or UDCA (15 mg/kg/BW). MC infiltration was measured by immunhistochemistry and quantitative polymerase chain reaction (qPCR) for c-Kit, chymase, and tr

SUBMITTER: Meng F 

PROVIDER: S-EPMC6214746 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature