Nonetheless, the ablation strategies employed in our study (1) avoid common side effects described for DC ablation due to our use of CD11c-DTR chimeric mice and 120G8 antibody, (2) address the role of both cDC and pDC, and (3) investigate the role of cDCs in
two common models of liver fibrosis. Our study contains several limitations. First, because we observed more than 1,400 HM-regulated genes, it is likely that genes besides NF-κB–regulated genes affect HSC responses. Further studies are required to unravel the relevance of NF-κB–independent genes and pathways regulated by HM. These may include additional mediators secreted from selleck chemicals HMs such as IL-6 and transforming growth factor β.[35, 42] Accordingly, our IPA analysis revealed Stat1/3/5 as an HM-activated pathway. Second, our studies were performed in mouse models, and further studies are required to determine whether HM-induced NF-κB activation plays a role in human fibrogenesis. As patients develop fibrosis slowly over decades, pathways that promote long-term myofibroblast survival may be particularly relevant. IL-1 and TNF inhibitors may be considered for antifibrotic therapies but may cause severe side effects. In conjunction with previous studies,[32, 43] our data support the concept that targeting the NF-κB pathway in HSCs and subsequent induction
that HMs provide a novel link between inflammation, HSC survival, and liver fibrosis and suggests that inflammatory signaling pathways may provide additional targets for antifibrotic therapies in the liver. Future studies are needed to determine whether macrophage-mediated promotion of myofibroblast survival also promotes fibrosis in other organs. Additional Supporting Information may be found in the online version of this article. “
“Background and Aim: Insulin resistance and diabetes mellitus (DM) are known to contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, the relationship between glucose metabolism and NAFLD is not well known. In this study, we investigated whether secretion patterns of glucose and insulin could influence the histological severity in NAFLD patients without prior known type 2 DM. Methods: A 75-g glucose tolerance test was performed on 173 biopsy-proven NAFLD patients without prior known type 2 DM. Plasma glucose and insulin levels were analyzed periodically for 3 h after oral glucose loading. Results: Of the 173 NAFLD patients, 168 had non-alcoholic steatohepatitis, whereas no patient had cirrhosis. Irrespective of the hemoglobin A1c levels, impaired glucose tolerance, including DM, was detected in 60% of the NAFLD patients.