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J Appl Physiol (January 27, 2005). doi:10.1152/japplphysiol.01220.2004
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Submitted on October 29, 2004
Accepted on January 25, 2005

TNF-{alpha}, but not IL-6, stimulates Plasminogen Activator Inhibitor 1 (PAI-1) Expression in Human Subcutaneous Adipose Tissue

Peter Plomgaard1, Pernille Keller1, Charlotte Keller1, and Bente Klarlund Pedersen1*

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

* To whom correspondence should be addressed. E-mail: BKP{at}rh.dk.

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




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