Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue.
Adipose tissue is the source of production and site of action of several pro- and antiinflammatory cytokines. We have recently shown that white adipose tissue (WAT) is a major producer of the antiinflammatory IL-1 receptor antagonist (IL-1Ra). Because IL-1Ra serum levels are elevated 7-fold in human obesity and an excess of this protein has been implicated in the acquired resistance to leptin and insulin, we investigated the regulation of IL-1Ra in human WAT. We demonstrate that IL-1Ra is mainly produced by adipocytes, rather than the stromal fraction of WAT, and that IL-1alpha and beta, as well as interferon-beta (IFN-beta), strongly up-regulate the expression and secretion of IL-1Ra in WAT. Moreover, human WAT expresses the receptors and proteins known to be required for the action of IL-1 (IL-1 receptor type I, IL-1 receptor accessory protein) and IFN-beta (IFN-alpha/beta receptor subunits 1 and 2). Finally, human WAT actively secretes these regulatory cytokines, suggesting that they up-regulate IL-1Ra through a local autocrine/paracrine action, which is hypothesized to play a regulatory role in adipogenesis and metabolism.
Juge-Aubry
Cristiana E
CE
Endocrine Unit, Department of Internal Medicine, University Hospital, CH-1211 Geneva 14, Switzerland.
Somm
Emmanuel
E
Chicheportiche
Rachel
R
Burger
Danielle
D
Pernin
Agnès
A
Cuénod-Pittet
Brigitte
B
Quinodoz
Pierre
P
Giusti
Vittorio
V
Dayer
Jean-Michel
JM
Meier
Christoph A
CA
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000494:pharmacology*; D016899:Interferon-beta / Q000235:genetics / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
C507763:IL1RN protein, human; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D015847:Interleukin-4; D016899:Interferon-beta