Activation of epithelial sodium channel in human middle ear epithelial cells by dexamethasone.
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.
Son
Eun Jin
EJ
Department of Otorhinolaryngology, National Medical Center, Seoul, South Korea.
Kim
Sung Hunh
SH
Park
Hun Yi
HY
Kim
Su Jin
SJ
Yoon
Joo-Heon
JH
Chung
Hyun Pil
HP
Choi
Jae Young
JY
D000042:Absorption / Q000187:drug effects; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004432:Ear, Middle / Q000166:cytology*; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D062708:Epithelial Sodium Channel Agonists; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D062708:Epithelial Sodium Channel Agonists; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D003907:Dexamethasone