Role of Cytokines in the Regulation of Plasminogen Activator Inhibitor-1 Expression and Secretion in Newly Differentiated Subcutaneous Human Adipocytes

M. Birgel, H. Gottschling-Zeller, K. Rohrig, H. Hauner
2000 Arteriosclerosis, Thrombosis and Vascular Biology  
Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are characteristic for obesity and are associated with increased risk of thromboembolic complications. PAI-1 recently was reported to be expressed and secreted by human adipocytes, but little is known about regulation of PAI-1 in human adipose tissue. Therefore, we examined the effects of selected cytokines present in adipose tissue on expression and secretion of PAI-1 in in vitro, differentiated subcutaneous human adipocytes in
more » ... y culture. Transforming growth factor-␤1 (TGF-␤1) increased PAI-1 secretion in a dose-and time-dependent manner. PAI-1 protein increased by 3.2-fold and PAI-1 mRNA by 1.9-fold after a 6-hour exposure to 400 pmol/L TGF-␤1. This effect is probably mediated by TGF-␤1 type 2 and 3 receptors, which were found to be expressed in cultured human adipocytes. Moreover, TNF-␣ and interkeukin-1␤ (IL-1␤) also exerted a stimulatory effect on PAI-1 release and increased PAI-1 mRNA levels. As assessed by a semiquantitative reverse transcriptionpolymerase chain reaction technique, TGF-␤1 mRNA is expressed by differentiation of human preadipocytes and is moderately upregulated by TNF-␣ and IL-1␤. In conclusion, our results clearly indicate that TGF-␤1 is a potent inducer of PAI-1 production in subcutaneous human adipocytes. In addition, data suggest that TNF-␣ and IL-1␤ also have stimulatory effects on PAI-1 protein secretion and may contribute to the elevated PAI-1 levels observed in obesity.
doi:10.1161/01.atv.20.6.1682 pmid:10845889 fatcat:jdvotm7e6jgd5ltylwg34knibq