Interleukin-6 upregulates glucocorticoid receptor numbers in human osteoblast-like cells.
Interactions between the endocrine and immune systems are well known with special regard to the hypothalamic-pituitary-adrenal axis. Little of the literature focuses on the complex effects of cytokines on tissue responsiveness to glucocorticoids (GC). In bone tissue, osteoblasts represent a valuable model for studying GC-cytokine interactions. Hence, we have studied two human osteosarcoma cell lines (Saos-2 and MG-63) with different degrees of differentiation and different constitutive IL-6 production (3.4 +/- 0.3 (mean +/- SE) and 3309 +/- 578 pg/10(6) cells). We measured glucocorticoid receptor (GR) number and affinity as a function of the exposure of cells to different amounts of IL-6. Incubation for 20 h with IL-6 at increasing concentrations up to 2000 pg/ml yielded a significant increase of GR binding sites in both cell lines. IL-6 was also able to reverse the inhibitory effect of dexamethasone (1 mumol/l) on GR in both cell lines. In MG-63 cells, expressing higher concentrations of GR, IL-6 deprivation via a specific anti-IL-6 antibody (100 ng/ml) significantly decreased GR. In Saos-2 cells, expressing lower concentrations of GR, a 40 h treatment with human IL-1 beta (10 ng/ml) significantly increased both IL-6 production and GR. This latter effect was completely abolished by co-treating the cells with the anti-IL-6 antibody. Our results provide evidence that IL-6 is an autocrine positive modulator of GR number in human osteoblasts.
Masera
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RG
Clinica Medica Generale and Farmacologia, Dipartimento di Scienze Cliniche e Biologiche, University of Turin, Regione Gonzole 10, 10043 Orbassano-Turin, Italy.
Dovio
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Sartori
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ML
Racca
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Angeli
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D001859:Bone Neoplasms; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000276:immunology; D012516:Osteosarcoma; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation
D007375:Interleukin-1; D015850:Interleukin-6; D011965:Receptors, Glucocorticoid