Regulation of plasminogen activitor inhibitor-1 in human adipose tissue: interaction between cytokines, cortisol and estrogen.
To investigate further the role of plasminogen activator inhibitor-1 (PAI-1) in human adipose tissue, the regulation of cytokines, cortisol (dexamethasone) as well as estrogen on PAI-1 were determined in human adipose tissue fragments. PAI-1 activity was increased in human adipose tissue fragments incubated for 48 h with interleukin-1beta (IL-1beta) (2.6-fold, p < 0.01) and tumor necrosis factor-alpha (2.3-fold, p < 0.01). Incubation with interleukin-6 revealed a non-significant decrease in PAI-1 activity. Parallel findings were obtained when studying the PAI-1 mRNA expression. Dexamethesone increased PAI-1 activity after incubation for 8 h (p < 0.05) and enhanced the stimulation of IL-1beta after 8 h incubation. However, after 24 and 48 h, dexamethasone significantly reduced the IL-1beta induced increase in PAI-1 activity by 24-52% (p < 0.05), accordingly, PAI-1 mRNA expression was reduced 60%. Finally, the induction of PAI-1 activity and PAI-1 mRNA expression by IL-1beta was attenuated by estrogen (17.8+/-4.9%, p < 0.05 and 20.9+/-5.8%, p < 0.05, respectively). These results indicate that multiple cytokines, estrogen and dexamethasone may be involved in the regulation of PAI-1 biosynthesis in human adipose tissue, and suggest that there are interactions between cytokines and these steroid hormones. The interplay between these hormones may be of importance for the levels of PAI-1 observed in obesity and associated states.
He
G
G
Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus University Hospital, Denmark.
Pedersen
S B
SB
Bruun
J M
JM
Richelsen
B
B
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D004967:Estrogens; D005938:Glucocorticoids; D007375:Interleukin-1; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D006854:Hydrocortisone