High glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells.

摘要: High glucose induces MCP-1 expression partly via tyrosine kinase–AP-1 pathway in peritoneal mesothelial cells. Background dialysis solutions has been implicated the pathogenesis of fibrosis chronic ambulatory (CAPD) patients. However, mechanisms are not very clear. Peritoneal macrophages seem to participate process and monocyte chemoattractant protein-1 (MCP-1) plays a key role recruitment monocytes toward cavity. little is known about effect high on its signal transduction human Methods Mesothelial cells were cultured with (5 100 mmol/L) or mannitol chronically for up seven days. mRNA protein was measured by Northern blot analysis enzyme-linked immunosorbent assay (ELISA). Chemotactic activity high-glucose–conditioned culture supernatant chemotactic assay. To examine roles transcription factors activator (AP-1) nuclear factor-κB (NF-κB), electrophoretic mobility shift (EMSA) performed. Results Glucose induced time- dose-dependent manner. cell supernant also increased. Equivalent concentrations had no significant effect. High-glucose–conditioned possessed an increased monocytes, which neutralized anti–MCP-1 antibody. EMSA revealed that AP-1 binding manner, but NF-κB. Curcumin, inhibitor AP-1, dose-dependently suppressed induction glucose. Tyrosine kinase inhibitors such as genistein (12.5 50 μmol/L) herbimycin A (0.1 1 inhibited high-glucose–induced activity. Conclusions kinase-AP-1 pathway.