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

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.