Tumour necrosis factor-mediated release of plasminogen activator inhibitor 1 by human peritoneal mesothelial cells

Abstract

Human mesothelial cells synthesize plasminogen activator inhibitor (PAI) 1 in inflamed peritoneal tissue. The role of tumour necrosis factor (TNF) in the mediation of this response was studied. Postoperative peritoneal drain fluid contained both TNF and PAI-1. Peak levels of TNF at 4 h (median 271 pg/ml) preceded a rise in PAI-1 concentration, which peaked at 18 h (median 943·1 ng/ml). Thus TNF may mediate increased PAI-1 release in inflamed peritoneum. TNF significantly increased the mean(s.e.m.) release of PAI-1 by human peritoneal mesothelial cells in vitro at 4 h (control 1·84(0·17) ng/μg versus TNF 2·37(0·17) ng/μg, P0·05), 6 h (2·53(0·09) versus 3·88(0·46) ng/μg, P<0·05), 18 h (0·50(0·02) versus 1·04(0·11) ng/μg, P<0·05) and 24 h (0·87(0·05) versus 1·35(0·11)ng/μg, P<0·05). TNF may be an important mediator of PAI-1 production by human mesothelial cells during peritoneal inflammation.