title: Glucocorticoids inhibit diastrophic dysplasia sulfate transporter activity in otosclerosis by interleukin-6.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  The authors conducted a prospective, case-control study.
  
  
  METHODS
  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.
  
  
  RESULTS
  : 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imauchi
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.forename: Pascale
authors.initials: P
authors.lastname: Lainé
authors.forename: Olivier
authors.initials: O
authors.lastname: Sterkers
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ferrary
authors.forename: Alexis Bozorg
authors.initials: AB
authors.lastname: Grayeli
mesh_terms: D000704:Analysis of Variance; D027321:Anion Transport Proteins; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D026901:Membrane Transport Proteins / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology; D010040:Otosclerosis / Q000378:metabolism*; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D005938:Glucocorticoids; D015850:Interleukin-6; D026901:Membrane Transport Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters; D015735:Mifepristone; D003907:Dexamethasone