© 2000 American Heart Association, Inc.
Thrombosis |
Role of Cytokines in the Regulation of Plasminogen Activator Inhibitor-1 Expression and Secretion in Newly Differentiated Subcutaneous Human Adipocytes
From the Diabetes Research Institute at the Heinrich-Heine-University, Düsseldorf, Germany.
Correspondence to H. Hauner, MD, Clinical Department, Diabetes Research Institute at the Heinrich-Heine-University, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail hauner{at}dfi.uni-duesseldorf.de
Abstract—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 primary culture.
Transforming growth factor-ß1 (TGF-ß1) 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-ß1. This effect is probably mediated by TGF-ß1 type 2 and 3
receptors, which were found to be expressed in cultured human
adipocytes. Moreover, TNF-
and interkeukin-1ß (IL-1ß) also
exerted a stimulatory effect on PAI-1 release and increased PAI-1 mRNA
levels. As assessed by a semiquantitative reverse
transcription—polymerase chain reaction technique, TGF-ß1 mRNA is
expressed by differentiation of human preadipocytes and is moderately
upregulated by TNF- and IL-1ß. In conclusion, our results clearly
indicate that TGF-ß1 is a potent inducer of PAI-1 production
in subcutaneous human adipocytes. In addition, data suggest that
TNF- and IL-1ß also have stimulatory effects on PAI-1 protein
secretion and may contribute to the elevated PAI-1 levels observed
in obesity.
Key Words: obesity • tumor necrosis factor • growth factors • interleukin • plasminogen activator inhibitor
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