eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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3/2010
vol. 35
 
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abstract:

Experimental immunology
Differential regulation of tumor necrosis factor a and transforming growth factor β production by the plasminogen activator inhibitor 1 in endothelial and cancer cells

Joanna Chorostowska-Wynimko
,
Marta Kędzior
,
Radosław Struniawski
,
Beata Gruber
,
Elżbieta Anuszewska
,
Ewa Skrzypczak-Jankun
,
Jerzy Jankun

(Centr Eur J Immunol 2010; 35 (3): 123-127)
Online publish date: 2010/10/05
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The plasminogen activator inhibitor (PAI-1) is the key component of fibrynolytic system, its synthesis is rapidly activated by cytokines and mediators driving inflammatory response, both acute and persistent low-grade. While tumor necrosis factor a (TNF-α) and transforming growth factor β (TGF-b) are established potent direct stimulators of PAI-1 production in numerous tissues, little is known of any feed-back regulation that might be accountable for effects of PAI-1 on their synthesis. Present study provides evidence for the existence of negative feed-back regulation between PAI-1 and its potent activator TGF-b in endothelial cells. Dose-dependent inhibition of TGF-b production was observed in HUVEC cultures with physiological (10 mg/ml) and supraphysiological (100 mg/ml) (p < 0.02) PAI-1 concentrations exerting significant suppressive effect in comparison to control (respectively p < 0.05; p < 0.02) as well as cultures spiked with subphysiological PAI-1 dose of 1 mg/ml (p < 0.0001; p < 0.02). No such regulation was demonstrated for cancer cells of lung and prostate origin which might implicate different regulatory mechanism in neoplastic cells. Similarly, no functional interplay between PAI-1 and TNF-α levels in 24 hrs cultures of any evaluated cell lines was observed.
keywords:

PAI-1, TNF-α, TGF-b, HUVECs, lung cancer cells, prostate cancer cells

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