Interleukin-1beta stimulates the production of extracellular matrix in cultured human peritoneal mesothelial cells

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Interleukin-1beta stimulates the production of extracellular matrix in cultured human peritoneal mesothelial cells

WS Yang, BS Kim, SK Lee, JS Park, and SB Kim

Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.

OBJECTIVE: To investigate the effect of interleukin-1beta (IL-1beta) on the production of extracellular matrix in cultured human peritoneal mesothelial cells (HPMCs). DESIGN: Cultured HPMCs were treated with or without IL-1beta. Cell morphology was observed. The expression of fibronectin, alpha1(I) procollagen, and transforming growth factor-beta1 (TGFbeta1) mRNAs was measured by Northern blot analysis. The cell surface expression of fibronectin and type I collagen was evaluated by immunofluorescent staining. Fibronectin and type I collagen in culture supernatant were measured by inhibition ELISA. RESULTS: Interleukin-1beta induced morphologic change in HPMCs from a cuboidal epithelioid shape into an elongated fibroblastoid shape.The elongated cells were positive for cytokeratin although they had a fibroblastoid appearance. Treatment of HPMCs with IL-1beta resulted in increased expression of both fibronectin and alpha1(I) pro-collagen mRNA in dose- and time-dependent manners. Immunofluorescent staining showed strong and diffuse cytoplasmic expression of fibronectin and type I collagen in the cells treated with IL-1beta, whereas only weak perinuclear cytoplasmic staining was noted in the cells on media alone. The concentrations of secreted fibronectin and type I collagen in culture supernatant were significantly higher in the cells treated with IL-1beta than in the control cells. IL-1beta also stimulated the expression of TGFbeta1 mRNA. However, IL-1beta-induced fibronectin mRNA expression was only partially blocked by neutralizing anti-TGFbeta antibody. CONCLUSION: Interleukin-1beta stimulated the production of extracellular matrix in cultured HPMCs along with the induction of morphologic changes.This may play a role in the development of peritoneal fibrosis caused by peritonitis or bioincompatible dialysate in continuous ambulatory peritoneal dialysis patients.

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