MODULATION OF PROFIBRINOLYTIC AND ANTIFIBRINOLYTIC PROPERTIES OF HUMAN PERITONEAL MESOTHELIAL CELLS BY TRANSFORMING-GROWTH-FACTOR BETA(1) (TGF-BETA(1)), TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND INTERLEUKIN-1-BETA (IL-1-BETA)

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