[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.


CONCLUSIONS
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.
Min
R
R
Department of Pulmonology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Li
S
S
Wang
H
H
Zhang
J
J
Wang
T
T
Yang
Y
Y
D000328:Adult; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D010994:Pleura / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha