Son Eun Jin, Kim Sung Hunh, Park Hun Yi, Kim Su Jin, Yoon Joo-Heon, Chung Hyun Pil, Choi Jae Young
Department of Otorhinolaryngology, National Medical Center, Seoul, South Korea.
Eur J Pharmacol. 2009 Jan 14;602(2-3):383-7. doi: 10.1016/j.ejphar.2008.11.012. Epub 2008 Nov 12.
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.
中耳上皮的功能是维持中耳腔无液体状态。中耳上皮离子和液体转运功能障碍与中耳腔积液的发病机制有关,中耳腔积液是分泌性中耳炎的特征。类固醇疗法治疗分泌性中耳炎的疗效仍存在争议,且中耳上皮跨上皮转运功能的假定调节作用尚未得到证实。研究了地塞米松对培养的正常人中耳上皮(NHMEE)细胞钠(Na⁺)转运和液体吸收能力的影响。地塞米松使阿米洛利敏感的短路电流(Isc)显著增加。地塞米松显著提高上皮钠通道(ENaC)α和β亚基的mRNA和蛋白质表达水平。此外,地塞米松处理后,ENaC依赖的液体吸收显著增加。总之,我们已表明地塞米松刺激NHMEE细胞中的ENaC活性和ENaC依赖的液体吸收。这些发现表明糖皮质激素可能通过刺激中耳上皮的Na⁺转运和液体清除而有益于分泌性中耳炎的治疗。