5) or mouse liver (Fig. 8). However, the literature suggests that HO-1 expression in response to ethanol may be dependent on the age of the animals studied.32, 33 In Kupffer cells, pharmacological Akt inhibitor inhibition of HO-1 or siRNA knockdown of HO-1 expression completely ameliorated the ability of gAcrp to inhibit LPS-stimulated TNF-α expression. Pharmacological induction of HO-1 in mice reduced LPS-stimulated TNF-α expression in the livers of ethanol-fed mice to that of pair-fed controls. Taken together, these data demonstrated a critical role for HO-1 in dampening the pro-inflammatory response
to LPS both in Kupffer cells and in vivo. In summary, these data provide strong evidence for an essential role of IL-10/STAT3/HO-1 in mediating the anti-inflammatory function of gAcrp, demonstrating that gAcrp-dependent responses use two critical anti-inflammatory pathways. Importantly, after chronic ethanol exposure, Kupffer cells exhibit an increased sensitivity to the anti-inflammatory
effects of both gAcrp and IL-10, and induction of HO-1 in vivo protects mice from the sensitizing effects of ethanol on LPS-stimulated TNF-α expression. The identification of HO-1 as a downstream effector of gAcrp provides an exciting path for the design and development of novel therapeutic approaches for the resolution of chronic inflammation associated with alcoholic liver disease. Additional Supporting Information may be found in the online AZD9668 research buy version of this article. “
“To reveal
the site of immunoglobulin (Ig)M production 3-mercaptopyruvate sulfurtransferase in primary biliary cirrhosis (PBC) we performed immunohistochemical analysis on spleens collected from patients with PBC. Splenic tissue samples were collected at the time of the autopsy from patients with hepatic failure. Immunostaining for IgM, CD21 and CXCL13 were performed using the splenic tissue samples. The samples from five out of eight cases with PBC but not in eight cases of chronic hepatitis C virus infection showed accumulation of IgM positive cells in CD21 positive lymph follicles. The CXCL13 positive cells also accumulated in the center of the lymph follicles where the IgM positive cells accumulated. The present results suggest that excess IgM is produced from the spleen of PBC. Furthermore, it was suggested that CXCL13 positive follicular dendritic cells possibly contribute to this process. PRIMARY BILIARY CIRRHOSIS (PBC) frequently occurs in middle aged or older women. The disease is marked by an appearance of antimitochondrial autoantibodies and high immunoglobulin (Ig)M level in blood.