These data indicate that IL-32 affects several parameters of HCV pathology but itself might not have antiviral properties. Other viral infections such as influenza A virus infection also induce IL-32 expression.18, 42 Influenza virus induced cyclooxygenase (COX)-2-mediated prostaglandin E2 production was suppressed by overexpression of IL-32 but decreased by IL-32-specific siRNA, suggesting a feedback mechanism between IL-32 selleck and COX-2.18 A clear antiviral effect against influenza A virus for IL-32 has not been demonstrated in these studies. In conclusion, in patients with chronic HCV the presence of IL-32

is associated with severity of steatosis, ITF2357 hepatic inflammation, and liver fibrosis. IL-32 is expressed by hepatocytes and up-regulated upon stimulation with IL-1β or TNF-α as well as HCV infection. Although IL-32 lacks anti-HCV activity at least in a cell culture

system, our data suggest that viral infection stimulates expression of this cytokine, thus supporting a role for IL-32 in chronic HCV infection and related pathologies. “
“This review focuses on the hypothesis that biliary HCO secretion in humans serves to maintain an alkaline pH near the apical surface of hepatocytes and cholangiocytes to prevent the uncontrolled membrane permeation of protonated glycine-conjugated bile acids. Functional impairment of this biliary HCO umbrella or its regulation may lead to enhanced vulnerability of cholangiocytes

and periportal hepatocytes toward the attack of apolar hydrophobic bile acids. An intact interplay of hepatocellular and cholangiocellular adenosine triphosphate (ATP) selleckchem secretion, ATP/P2Y- and bile salt/TGR5-mediated Cl−/ HCO exchange and HCO secretion, and alkaline phosphatase–mediated ATP breakdown may guarantee a stable biliary HCO umbrella under physiological conditions. Genetic and acquired functional defects leading to destabilization of the biliary HCO umbrella may contribute to development and progression of various forms of fibrosing/sclerosing cholangitis. (HEPATOLOGY 2010) The pathogenesis of chronic cholestatic liver diseases such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and other fibrosing cholangiopathies remains enigmatic.1 Without adequate therapy, the prognosis is dismal and current treatment strategies may achieve stabilization but no resolution.1 Genetic factors contribute to the development of chronic cholestatic liver disease as indicated by sibling studies in PBC.2 An increased risk for first-degree relatives of PBC and PSC patients to develop the same disease also indicate a genetic background. Notably, various mutations of genes involved in bile formation present with a sclerosing/fibrosing cholangitis-like phenotype.