Evidence for autocrine regulation of glucocorticoid receptors by interleukin-6 in human osteoblast-like cells

Journal/Book: Z Rheumatol 1999; 58: 309. 1999;

Abstract: M. L. Sartori; Universita di Torino Dipartimento Di Scienze Cliniche E Biologiche Cattedra di Medicina Interna Divisione Universitaria di Clinica Medica Generale Azienda Ospedaliera San Luigi Gonzaga Orbassano - Torino Osteoblast-osteoclast interplay is constantly under the influence of local bone-derived molecules cytokines and growth factors among others and of systemic hormones. Interleukin (IL)-6 released from osteoblasts/stromal cells plays an important role in bone resorption. It acts primarily on osteoclast progenitors to stimulate both proliferation and differentiation. Glucocorticoids are potent osteopenic agents acting both on mineral metabolism and on bone cells. They inhibit bone formation rather than stimulate bone resorption. In fact via specific receptors they decrease osteoblast number and activity including cytokine and growth factor production. While the role of glucocorticoids in regulating cytokine production and action has been extensively investigated very little information is available about cytokine effects on glucocorticoid action and glucocorticoid-receptor interaction in sensitive cellular targets. The present study was designed to investigate the effects of IL-6 on glucocorticoid receptor (GR) number in osteoblast-like cultured cells. Two human osteosarcoma cell lines with different degree of differentiation Saos-2 and MG-63 (more differentiated) were maintained in appropriate medium. For experiments Saos-2 and MG-63 cells were treated for 20 h with dexamethasone (1 µmol/L). Thereafter aliquots of both cell lines were washed and exposed to increasing concentrations of human recombinant IL-6 for additional 20 h (concentration range: 100-2000 pg/mL). Concomitantly Saos-2 and MG-63 cells that were not pre-treated with dexamethasone were exposed for 20 h to the cytokine at the same concentration range. GR number was measured in all experimental conditions by 3H-dexamethasone radioligand-binding assay; Scatchard analysis was used to obtain glucocorticoid receptor binding parameters/cell. ... le

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