Anti-Collagen Type IV polyclonal antibody

Hepatitis C virus (HCV) infection and its recurrence after orthotopic liver transplantation (OLT) are associated with the remodeling of extracellular matrix (ECM) components [ particularly collagen (Col)], which leads to fibrosis. Our aim was to determine whether the development of antibodies (Abs) to self-antigen Col in HCV-infected patients correlates with the fibrosis stage and the peripheral cytokine response. Patients with chronic HCV infection, patients with HCV recurrence after OLT who had undergone a biopsy procedure, and healthy control subjects were enrolled. The HCV subjects (n = 70) were stratified as follows: (1) a non-OLT group without fibrosis (Scheuer stages 0-2), (2) a non-OLT group with fibrosis (Scheuer stages 3-4), (3) a post-OLT group without fibrosis (Scheuer stages 0-2), and (4) a post-OLT group with fibrosis (Scheuer stages 3-4). Serum samples were analyzed for Abs against Col1, Col2, Col4, Col5, and vimentin with enzyme-linked immunosorbent assays. Serum levels of cytokines were measured with multiplex bead immunoassays. The levels of Abs to Col1 were higher in the fibrosis groups versus the no-fibrosis groups and the controls for both non-OLT patients (P < 0.001) and post-OLT patients (P = 0.01). There were increased levels of Abs to Col2, Col4, Col5, and vimentin in the non-OLT fibrosis group (Col2, P = 0.0001; Col4, P = 0.122; Col5, P < 0.0001; vimentin, P = 0.36) and in the post-OLT fibrosis group (Col2, P = 0.006; Col4, P = 0.19; Col5, P < 0.0001; vimentin, P = 0.24) in comparison with the no-fibrosis groups. The non-OLT and post-OLT fibrosis groups demonstrated significantly higher T helper 2 (T(h)2) and T helper 17 (T(h)17) cytokine levels and lower T helper 1 cytokine levels in comparison with the no-fibrosis groups. Our results demonstrate that in HCV-infected patients, the levels of Abs to ECM Col1, Col2, and Col5 positively correlate with liver fibrosis, which is associated with a predominantly Th2 and Th17 cytokine profile. Liver Transpl 17:814-823, 2011. (C) 2011 AASLD.

Hyperglycemia induced endothelial injury is a key pathogenetic factor in diabetic cardiomyopathy. In diabetes, changes in pro-inflammatory cytokines are a key mechanism leading to cardiac fibrosis. We have previously demonstrated alteration of miR-146a in chronic diabetic complications. Here, we investigated the role of endothelial miR-146a in mediating inflammation and fibrosis in diabetic cardiomyopathy. To examine the effects of miR-146a on the inflammatory mediators, an endothelial specific miR-146a overexpressing transgenic mice (TG) using tie-2 promoter, was generated. We examined these mice and wild type littermate controls with or without STZ induced diabetes. Transthoracic echocardiography was performed. Cardiac tissues were examined for inflammatory cytokine mRNAs and proteins by real time RT-PCR or ELISA. Cardiac fibrosis was examined by histology staining. Human cardiac microvascular endothelial cells (HCMECs) and primary endothelial cells isolated from mice were used following incubation with various levels of glucose with or without miR-146a mimics or antagomir transfection. In hearts of wild type mice with diabetes, increased expression of inflammatory markers and extracellular matrix proteins (IL6, TNF alpha, IL-1 beta, MCP-1, NF-kappa B, Col1 alpha l, Col4 alpha 1) were seen compared to wild type controls. These changes were prevented in the diabetic TG mice. In addition, WT diabetic mice showed cardiac functional abnormalities, which were improved in the diabetic TG mice. In vitro studies showed glucose induced increase the expressions of the above inflammatory cytokines and specific NF-kappa B regulators (IRAK1 &TRAF6). Such changes were corrected in the HCMECs following miR-146a mimic transfection. These data indicate that in diabetes, increased inflammatory cytokine and extracellular matrix protein productions and associated cardiac functional alterations are regulated by endothelial miR-146a. Identification of such mechanisms may potentially lead to the development of novel RNA based therapeutics. (C) 2017 Published by Elsevier Ltd.