Interleukin-1β Stimulates the Production of Extracellular Matrix in Cultured Human Peritoneal Mesothelial Cells

Abstract

Objective

To investigate the effect of interleukin-1β (IL-1β) on the production of extracellular matrix in cultured human peritoneal mesothelial cells (HPMCs).

Design

Cultured HPMCs were treated with or without IL-1β. Cell morphology was observed. The expression of fibronectin, α1(I) procollagen, and transforming growth factor-β1 (TGFβ1) 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-1β 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-1β resulted in increased expression of both fibronectin and α1(I) procollagen 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-1β, 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-1β than in the control cells. IL-1β also stimulated the expression of TGFβ1 mRNA. However, IL-1β-induced fibronectin mRNA expression was only partially blocked by neutralizing anti-TGFβ antibody.

Conclusion

Interleukin-1β 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.