title: Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function.
abstract: Adipocytes produce the inflammatory cytokine interleukin-6 (IL-6); however, it is not known whether these cells express the IL-6 receptor system, how the secretion of this cytokine is regulated, and whether it has a function within adipose tissue. Using cultured human breast adipocytes, we investigated the expression of IL-6 and its receptor system, the effects of IL-6 on main adipocyte functions, and the regulation of IL-6 secretion by catecholamines and glucocorticoids. In the culture system, immunohistochemistry demonstrated expression of IL-6 and its receptor system, consisting of the ligand-binding IL-6 receptor and the signal-transducing protein gp130, in mature adipocytes, but not in undifferentiated adipocyte precursor cells. In freshly isolated adipocytes, RT-PCR detected messenger ribonucleic acids encoding the above proteins. Chronic incubation of adipocytes with 1 nmol/L IL-6 during adipose differentiation reduced glycero-3-phosphate dehydrogenase (GPDH) activity, a marker of adipocyte differentiation, and triglyceride synthesis to 67 +/- 9% of the basal level (mean +/- SEM; P < 0.05) only on day 21. Incubation of differentiated adipocytes with 10 nmol/L IL-6 for 24 h also resulted in a reduction of GPDH activity to 81 +/- 5% (P < 0.05). On the other hand, 24-h exposure to 10 nmol/L IL-6 increased basal glycerol release by 42 +/- 12% (P < 0.01) and isoproterenol-induced glycerol release by 21 +/- 6% (P < 0.05). The same concentration of IL-6, however, did not alter basal or insulin-stimulated glucose transport. IL-6 secretion was acutely and chronically stimulated by 1 micromol/L isoproterenol (peak of 6.2-fold after 3 h; P < 0.001) and only moderately suppressed by 100 nmol/L cortisol (-36 +/- 10%; P < 0.001). In conclusion, human breast adipocytes release substantial amounts of IL-6 and express IL-6 receptor and gp130. The secretion of IL-6 by adipocytes is strongly stimulated by beta-adrenergic activation and is modestly suppressed by glucocorticoids. IL-6 reduces GPDH activity and stimulates lipolysis, suggesting an autocrine/paracrine role of this cytokine in human adipose breast tissue.
authors.affiliation: German Diabetes Research Institute, 40225 Dusseldorf.
authors.forename: G
authors.initials: G
authors.lastname: Päth
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: M
authors.initials: M
authors.lastname: Gurniak
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: W A
authors.initials: WA
authors.lastname: Scherbaum
authors.forename: H
authors.initials: H
authors.lastname: Hauner
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D001940:Breast / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011943:Receptors, Adrenergic, beta; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D006854:Hydrocortisone