38 In that study, CS exposure was associated with increased ALT. Future studies are needed to better elucidate the mechanistic aspects of the effects of CS in NAFLD and to better characterize the Nutlin-3 cell line role of CS in human NAFLD. Nonetheless, this study provides one more reminder that there is already ample experimental

and clinical evidence consistently pointing in the same direction: CS aggravates liver injury in CLD. It is time to take the harmful effects of CS in CLD more seriously. As hepatologists, we need to incorporate the intake of a more thorough smoking history during our evaluations, educate our patients on the effects of this modifiable risk factor on liver injury, and strongly recommend smoking cessation Small molecule library research buy in all patients with CLD. “
“Dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) mice, expressing a dominant negative form of TGFβ receptor II under control of the CD4 promoter, develop autoimmune colitis and cholangitis. Deficiency in interleukin (IL)-12p40

lead to a marked diminution of inflammation in both the colon and the liver. To distinguish whether IL-12p40 mediates protection by the IL-12 or IL-23 pathways, we generated an IL-23p19−/− dnTGFβRII strain deficient in IL-23, but not in IL-12; mice were longitudinally followed for changes in the natural history of disease and immune responses. Interestingly, IL-23p19−/− mice demonstrate dramatic improvement in their colitis, but no changes in biliary pathology; mice also manifest reduced T-helper (Th)17 cell populations and unchanged IFN-γ levels. We submit that the IL-12/Th1 pathway is essential for biliary disease pathogenesis, whereas the IL-23/Th17 pathway mediates colitis. To further assess the mechanism

of the IL-23-mediated protection from colitis, we generated an IL-17A−/− dnTGFβRII strain deficient in IL-17, a major effector cytokine produced by IL-23-dependent Th17 cells. Deletion of the IL-17A gene did not affect the severity of either cholangitis or colitis, suggesting 上海皓元 that the IL-23/Th17 pathway contributes to colon disease in an IL-17-independent manner. These results affirm that the IL-12/Th1 pathway is critical to biliary pathology in dnTGFβRII mice, whereas colitis is caused by a direct effect of IL-23. (HEPATOLOGY 2012) Murine strains with a deficiency in specific cytokine pathways are important tools for investigating the mechanism of immunopathogenesis of autoimmunity. Mice transgenic for directed expression of a dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII), under the control of the CD4 promoter lacking the CD8 silencer, spontaneously develop an inflammatory bowel disease (IBD).