Effect of IFN-α on extracellular matrix synthesis by humen peritoneal mesothelial cells under the condition of high glucose

Objective Human peritoneal mesothelial cells (HPMCs)are important components of the peritoneum and play a very important role in peritoneal dialysis (PD) and peritoneal fibrosis caused by peritoneal dialysis. The physiomorphological alteration of PD related peritoneal fibrosis is marked by the loss of peritoneal mesothelial cell layer and the accumulation of extracellular matrix (ECM). And during the two processes, HPMCs are not only passive sufferers, but also active participants. In the incompatible physiological environment induced by the peritoneal dialysate, HPMCs are injured and their proliferations are suppressed. They also secret ECM and ECM accumulating cytokines including the most important cytokine among them: transforming growth factor- α1 (TGF- α1).In this study, we investigated the effect of interferon- α(IFN- α) on the secretion of fibronectin (FN)、transforming growth factor- β1 (TGF- β1)、matrix metalloproteinases (MMP- 2) in human peritoneal mesothelial cells (HPMCs) under the condition of high glucose concentration trying to understand the significance of IFN- αon the prevention and treating of peritoneal fibrosis caused by peritoneal dialysis. Methods HPMCs were isolated from discarded peritoneal dialysate which comed from the patients who were receiving continuous ambulatory peritoneal dialysis,and primarily cultured .The secondarily cultured HPMCs were used in the experiment. We can make cellular evaluation based on observation of the cells by light microscope and based on staining of immuno-histochemical methed with antibody for vimentin,cytokeratin8,factor Ⅷ. HPMCs were divided into experimental groups and control group.The experimental groups were treated with 2.5% glucose and IFN-αof different concentrations. The supernate was collected after 24h, 48h and 72h to detect FN、TGF- β1、MMP-2 in it. Results 1.HPMCs: The cultured HPMCs were spindly at first. About a week later, they connected with each other and took on a slabstone-like appearance. Immunohistochemistry analysis showed positive immunoreactivity of vimentin and cytokeratin and negative immunoreactivity of factor Ⅷ in these cells. 2.The FN-like and the TGF- β1-like immunoreactivity in all the experimental groups treated with 2.5% glucose was significantly higher than that in the control group (P 0.05). The FN-like and the TGF-β1-like immunoreactivity in groups treated with 2.5% glucose and IFN-αwas significantly lower than that in groups treated with 2.5% glucose only (P 0.05); IFN- α reduced the synthesis of FN TGF- β1 in a dose- dependent manner. MMP-2: There is no marked difference between control group and experiment groups. Conclusions Glucose of high concentration can promote the synthesis of FN、TGF-β1 but has no effect on the synthesis of MMP-2 in HPMCs. IFN- αcan reverse these changes. IFN- αis likely to reduce the accumulation of ECM in CAPD and it has certain significance in the prevention and treating of peritoneal fibrosis.