[Cytokine-induced release of plasminogen activator inhibitor-1 by human pleural mesothelial cells].

OBJECTIVE

To investigate the effects of inflammatory cytokines on the production of plasminogen activator inhibitor-1 (PAI-1) by human pleural mesothelial cells (HPMC).

METHODS

Six primary cultures of HPMC isolated from patients with exudative pleural effusion were incubated in DMEM/F12 medium to examine the effect of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha) or transforming growth factor-beta1 (TGF-beta1) on the fibrinolytic properties of HPMC in vitro. The purity of the cell population was assessed by morphologic, ultrastructural and immunohistochemical characteristics. PAI-1 activity in the conditioned media of third passage HPMC was detected using chromogenic substrate method.

RESULTS

As compared with the controls, PAI-1 activity in the conditioned media of HPMC increased significantly by stimulation with IL-1beta, TNFalpha or TGF-beta1 for 24 hours at the level of 0.20 microg/L (IL-1beta: q = 3.38, P < 0.05; TNFalpha: q = 4.41, P < 0.05; TGF-beta1: q = 22.03, P < 0.01), 2.00 microg/L (IL-1beta: q = 12.28, P < 0.01; TNFalpha: q = 16.60, P < 0.01; TGF-beta1: q = 19.23, P < 0.01) and 20.00 microg/L(IL-1beta: q = 24.30, P < 0.01; TNFalpha: q = 25.00, P < 0.01; TGF-beta1: q = 49.30, P < 0.01). Furthermore, HPMC responses to TGF-beta1 were significantly greater than those to IL-1beta or TNFalpha.

CONCLUSION

These results suggest that inflammatory cytokines might mediate the release of PAI-1 by HPMC in vivo, affect the deposition of fibrin within the pleural cavity and favor fibrogenesis.