Differential regulation of tumor necrosis factor alpha and transforming growth factor beta production by the plasminogen activator inhibitor 1 in endothelial and cancer cells

作者：Chorostowska Wynimko Joanna^*; Kedzior Marta; Struniawski Radoslaw; Gruber Beata; Anuszewska Elzbieta; Skrzypczak Jankun Ewa; Jankun Jerzy

来源：Central European Journal of Immunology, 2010, 35(3): 123-127.

• PAI-1
• TNF-alpha
• TGF-beta
• HUVECs
• lung cancer cells
• prostate cancer cells

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 alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) are established potent direct stimulators of PAI-1 production in numerous tissues, little is known of any feedback 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-beta in endothelial cells. Dose-dependent inhibition of TGF-beta production was observed in HUVEC cultures with physiological (10 mu g/ml) and supraphysiological (100 mu g/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 mu g/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-alpha levels in 24 hrs cultures of any evaluated cell lines was observed.

• 出版日期2010