Glucocorticoids Inhibit Diastrophic Dysplasia Sulfate Transporter Activity in Otosclerosis by Interleukin‐6

Abstract

Otosclerosis is a bone remodeling disorder localized to the otic capsule and associated with inflammation. In vitro, increased activity of the diastrophic dysplasia sulfate transporter (DTDST), which is implicated in bone metabolism, has been reported. Because glucocorticoids modulate the bone turnover and inhibit inflammatory processes, we investigated the effect of dexamethasone (Dex) on interleukin-6 and DTDST in otosclerosis. The authors conducted a prospective, case-control study. Primary cell cultures were obtained from stapes and external auditory canals in otosclerosis (n = 21) and control patients (n = 18). Assays with [H]Dex evaluated specific binding sites in otosclerotic and control stapes. The effects of Dex (10 to 10 M) and RU486 (10 M), a glucocorticoid antagonist, were studied on DTDST activity by sulfate uptake. IL-6 secretion was measured in culture media before and after Dex (10 M, 24 hours). The effect of IL-6 (10 M, 24 hours) was assessed on DTDST activity in control stapes. : The number of specific Dex-binding sites was similar in all stapedial cultures. Dex inhibited DTDST activity (19.4 +/- 1.02 vs. 29.4 +/- 3.94 pmol/microg prot/5 minutes) only in otosclerotic stapes. This effect was dose-dependent, antagonized by RU 486 and only observed 24 hours after Dex exposure. Interleukin (IL)-6 stimulated DTDST activity in normal stapes, whereas Dex inhibited IL-6 production only in otosclerotic stapes. Dex inhibits the DTDST activity, at least in part, through a reduction of IL-6 secretion only in otosclerotic cells. This effect is mediated through the glucocorticoid receptors and may lead to the reduction of bone turnover.