TNF-alpha, but not IL-6, stimulates plasminogen activator inhibitor-1 expression in human subcutaneous adipose tissue.
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-alpha 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-alpha (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-alpha and IL-6 reached 18 and 99 pg/ml, respectively, during the infusions. During the TNF-alpha 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-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.
Plomgaard
Peter
P
Copenhagen Muscle Research Centre, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Keller
Pernille
P
Keller
Charlotte
C
Pedersen
Bente Klarlund
BK
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007261:Infusions, Intra-Arterial; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000378:metabolism*
D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha