Modulation of middle ear epithelial function by steroids: clinical relevance.
The efficacy of steroid therapy for the treatment of otitis media in children remains controversial, and a putative modulation of the middle ear epithelial function has to be demonstrated. Using the MESV cell line, short-circuit current (ISC) technique was used to evaluate changes in ion transport induced by glucocorticoids. Dexamethasone (DXM) produced a dose- and time-dependent increase in ISC in MESV cells. This effect was inhibited by specific glucocorticoid antagonist (RU-38486) and was related to a sodium transport, since the DXM-induced increase in ISC could be prevented or abolished i) by apical addition of the specific Na+ channel inhibitor benzamil; or ii) by substitution of sodium with N-Methyl-glucamine in the incubation medium. RNase protection assay revealed that DXM increased the expression of the alpha subunit sodium channel mRNA, which changes paralleled the modulation of ion transport. These data demonstrate that steroids up-regulate the trans-epithelial sodium transport in the middle ear epithelium. As far as these experimental data can be extrapolated to the in vivo situation, a component of the beneficial effect of steroid therapy for the treatment of otitis media may result from a corticosteroid-induced improvement in fluid clearance from the middle ear.
Tan
C T
CT
Laboratoire d'Otologie Expérimentale, Faculté Lariboisière-St-Louis, Université Paris VII, France.
Escoubet
B
B
Van den Abbeele
T
T
Friedlander
G
G
Tran Ba Huy
P
P
Herman
P
P
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004432:Ear, Middle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D010033:Otitis Media / Q000188:drug therapy; D010042:Ouabain / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics; D015854:Up-Regulation
D005938:Glucocorticoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D012414:Rubidium Radioisotopes; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C013407:benzamil; D015735:Mifepristone; D010042:Ouabain; D000584:Amiloride; D003907:Dexamethasone