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Autocrine up-regulation of glucocorticoid receptors by interleukin-6 in human osteoblast-like cells.

Abstract：

:Interleukin (IL)-6 is a bone-resorbing cytokine that acts primarily on osteoclast progenitors to stimulate both proliferation and differentiation. Glucocorticoids (GC) down-regulate IL-6 synthesis in different cell types, including osteoblasts. Given the fact that bone remodeling is a tightly controlled process, it is reasonable to think of auto-regulatory mechanisms in the bone microenvironment able to prevent excess IL-6 production. 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 +/- 0.2 (mean +/- SE) and 2,898 +/- 401 pg/10(6) cells, respectively). We measured the expression of glucocorticoid receptor (GR) in terms of specific binding sites after exposure of cells to different amounts of IL-6. Incubation for 20 hours with IL-6 at increasing concentrations up to 2,000 pg/ml yielded significant increase of GR binding sites in both cell lines. IL-6 was also able to revert the inhibitory effect of dexamethasone (1 microM) on GR in both cell lines. In MG-63 cells, that express higher concentrations of GR, IL-6 deprivation via a specific anti-IL-6 antibody (100 ng/ml) significantly decreased GR, as it was noticed, although to a lesser degree, using a specific anti-IL-6 receptor antibody. In Saos-2, cells that express lower concentrations of GR, a 40-hour treatment with human IL-1beta (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 data are consistent with an autocrine up-regulation of GR expression by IL-6 in human osteoblast-like cells. This phenomenon, which is also relevant to paracrine cell-to-cell communication, subserves a feedback loop in the bone microenvironment that restrains excess inducible IL-6 production. In patients having high levels of IL-6 and given GCs, it could offer an additional explanation for the biphasic pattern of bone loss in the course of therapy.

journal_name

Calcif Tissue Int

journal_title

Calcified tissue international

authors

Dovio A,Masera RG,Sartori ML,Racca S,Angeli A

doi

10.1007/s00223-001-2024-8

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

293-8

issue

eissn

0171-967X

issn

1432-0827

journal_volume

pub_type

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Autocrine up-regulation of glucocorticoid receptors by interleukin-6 in human osteoblast-like cells.