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TNF-, but not IL-6, stimulates plasminogen activator inhibitor-1 expression in human subcutaneous adipose tissue

The Copenhagen Muscle Research Centre, and The Department of Infectious Diseases, Rigshospitalet, Denmark

Submitted 29 October 2004 ; accepted in final form 25 January 2005

Plasminogen activator inhibitor-1 (PAI-1) is produced by adipose tissue, and elevated PAI-1 levels in plasma are a risk factor in the metabolic syndrome. We investigated the regulatory effects of TNF- and IL-6 on PAI-1 gene induction in human adipose tissue. Twenty healthy men underwent a 3-h infusion of either recombinant human TNF- (n = 8), recombinant human IL-6 (n = 6), or vehicle (n = 6). Biopsies were obtained from the subcutaneous abdominal adipose tissue at preinfusion, at 1, 2, and 3 h during the infusion, and at 2 h after the infusion. The mRNA expression of PAI-1 in the adipose tissue was measured using real-time PCR. The plasma levels of TNF- and IL-6 reached 18 and 99 pg/ml, respectively, during the infusions. During the TNF- infusion, adipose PAI-1 mRNA expression increased 2.5-fold at 1 h, 6-fold at 2 h, 9-fold at 3 h, and declined to 2-fold 2 h after the infusion stopped but did not change during IL-6 infusion and vehicle. These data demonstrate that TNF- rather than IL-6 stimulates an increase in PAI-1 mRNA in the subcutaneous adipose tissue, suggesting that TNF- may be involved in the pathogenesis of related metabolic disorders.

human; subcutaneous adipose tissue; in vivo; gene expression; plasminogen activator inhibitor type I

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