Modulation of pro- and antifibrinolytic properties of human peritoneal mesothelial cells by transforming growth factor beta1 (TGF-beta1), tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta).

ABSTRACT

A decreased fibrinolytic activity of serosal surfaces appears to be a major factor in the development of peritoneal fibrous adhesions. Serosal fibrinolysis is regulated by mesothelial release of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2). We investigated the influence of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta1) and interleukin 1beta (IL-1beta) on pro- and antifibrinolytic properties of mesothelial cells (HOMC) using a cell/fibrin clot assay. TGF-beta1, TNF-alpha and IL-1beta induced a dose dependent 2.9, 2.3 and 1.9-fold increase of PAI-1 antigen, respectively, whereas t-PA concentrations decreased to one third of the control values. This modified PAI-1/t-PA secretion pattern leads to a significant delay of fibrinolysis. Analysis of m-RNA levels revealed increased PAI-1 m-RNA concentrations after 12 h and decreased m-RNA concentrations for t-PA after 6 h. Serosal hypofibrinolysis during peritonitis may be explained at least in part by cytokine effects which thus may favor adhesion formation.