Activation of epithelial sodium channel in human middle ear epithelial cells by dexamethasone.

Abstract

The middle ear epithelium functions to maintain a fluid-free middle ear cavity. Dysfunction of the middle ear epithelial ion and fluid transport is implicated in the pathogenesis of fluid collection in the middle ear cavity, characteristic of otitis media with effusion. The efficacy of steroid therapy for the treatment of otitis media with effusion remains controversial, and postulated modulation of transepithelial transport function in middle ear epithelia has yet to be demonstrated. The effect of dexamethasone on Na(+) transport and fluid absorption capacity was investigated in cultured normal human middle ear epithelial (NHMEE) cells. Dexamethasone produced a significant increase in amiloride-sensitive short-circuit current (Isc). Dexamethasone significantly increased expression levels of mRNAs and proteins of Epithelial Sodium Channel (ENaC)-alpha and -beta subunits. In addition, the ENaC-dependent fluid absorption was significantly increased after dexamethasone treatment. In summary, we have shown that dexamethasone stimulates ENaC activity and ENaC-dependent fluid absorption in NHMEE cells. These findings suggest glucocorticosteroids may be beneficial in treatment of otitis media with effusion by stimulating Na(+) transport and fluid clearance in the middle ear epithelia.