These therapies most often include fluconazole for candida, acyclovir for HSV and ganciclovir or foscarnet for CMV. Other rare infections include mycobacteria, other bacteria, actinomycosis and other virial, fungal and protozoal infections. “
“Aberrant expression of the chemokine CXC chemokine ligand (CXCL)10 has been linked to the severity of hepatitis C virus (HCV)-induced

liver injury, but the underlying molecular mechanisms remain Selleckchem Everolimus unclear. In this study, we describe a yet-unknown proapoptotic effect of CXCL10 in hepatocytes, which is not mediated through its cognate chemokine receptor, but the lipopolysaccharide receptor Toll-like receptor 4 (TLR4). To this end, we investigated the link of CXCL10 expression selleck products with apoptosis in HCV-infected patients and in murine liver injury models. Mice were treated with CXCL10 or neutralizing antibody to systematically analyze effects on hepatocellular apoptosis in vivo. Direct proapoptotic functions of CXCL10 on different liver cell types were evaluated in detail in vitro. The results showed that CXCL10 expression was positively correlated with liver cell apoptosis in humans and mice. Neutralization of CXCL10

ameliorated concanavalin A–induced tissue injury in vivo, which was strongly associated with reduced liver cell apoptosis. In vitro, CXCL10 mediated the apoptosis of hepatocytes involving TLR4, but not CXC chemokine receptor 3 signaling. Specifically, CXCL10 induced long-term protein kinase B and Jun N-terminal kinase activation, leading to hepatocyte apoptosis by caspase-8, caspase-3, and p21-activated kinase

2 cleavage. Accordingly, systemic application of CXCL10 led to TLR4-induced liver cell apoptosis in vivo. Conclusion: The results identify CXCL10 and its noncognate receptor, TLR4, as a proapoptotic signaling cascade during liver injury. Antagonism of the CXCL10/TLR4 pathway might be a therapeutic option in liver diseases associated with increased Y-27632 mw apoptosis. (HEPATOLOGY 2013) Acute hepatitis, cirrhosis, and hepatocellular carcinoma are associated with acute or chronic loss of hepatocellular integrity, which leads to increased mortality in many affected patients.1 Despite different causes of liver cell injury, a major mechanism leading to hepatic dysfunction is hepatocyte apoptosis.2 Thus, a better understanding of programmed cell death within the liver appears important to develop new therapeutic options for many different disease entities. However, the molecular mediators controlling hepatocyte apoptosis have not been fully deciphered in vivo and in vitro. In recent years, the contribution of chemokines to acute and chronic liver diseases has been reported in patients and in animal models.3 Chemokines are a class of small (8-12-kDa) chemotactic cytokines orchestrating the influx of immune cells into sites of inflammation, but also directly affect the biology of resident cells.