Interleukin-6 upregulates glucocorticoid receptor numbers in human osteoblast-like cells

• Published in: Zeitschrift für Rheumatologie Vol. 59 Suppl 2; no. S2; pp. II/103 - 107
• Main Authors: Masera, R G, Dovio, A, Sartori, M L, Racca, S, Angeli, A
• Format: Journal Article
• Language: English
• Published: Germany 01-01-2000
• Subjects: Bone Neoplasms; Dose-Response Relationship, Drug; Humans; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Osteoblasts - drug effects; Osteoblasts - immunology; Osteosarcoma; Receptors, Glucocorticoid - drug effects; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - immunology; Up-Regulation
• ISSN: 0340-1855
• DOI: 10.1007/s003930070003

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.