Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media.
Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media.
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DOI：
10.1016/j.ijporl.2016.06.056
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发表时间：
2016-09
影响因子：
1.5
通讯作者：
Kerschner JE
中科院分区：
文献类型：
--
作者：
Samuels TL;Yan J;Khampang P;MacKinnon A;Hong W;Johnston N;Kerschner JE
中耳细菌性中耳炎病原体激活的 Toll 样受体信号传导在 OM 易感性、发病机制和恢复中发挥关键作用。最近的研究表明，microRNA 146 (miR-146) 在多种组织中通过 Toll 样受体信号传导 (TLR) 的负反馈来调节炎症，但其在中耳炎中的作用尚不清楚。用促炎细胞因子、白细胞介素 1 β 或肿瘤坏死因子 α 刺激人中耳上皮细胞 2 至 24 小时。从患有渗出性中耳炎的儿童（n = 20）、复发性中耳炎（n = 9）和接受人工耳蜗植入的对照受试者（n = 10）中收集中耳活检。通过定量PCR（qPCR）测定miR-146a、miR-146b表达。通过 qPCR 在中耳活检中检测参与 TLR 信号转导的 miR-146 靶标、IRAK1 和 TRAF6 的表达。由经过认证的病理学家对中耳活检进行冷冻切片并测量上皮厚度。促炎细胞因子在体外诱导中耳上皮细胞中 miR-146 的表达。相对于对照受试者，中耳炎患者中耳 miR-146a 和 miR-146b 表达升高，并且与中耳上皮厚度相关。在临床人群中观察到 miR-146 和 TRAF6 表达之间呈负相关趋势。该报告是第一份评估 OM 临床人群中 miRNA 表达的报告。本文的研究结果表明 miR-146 可能在 OM 中发挥作用。
Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interluekin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours. Middle ear biopsies were collected from children with otitis media with effusion (n=20), recurrent otitis media (n=9), and control subjects undergoing cochlear implantation (n=10). miR-146a, miR-146b expression was assayed by quantitative PCR (qPCR). Expression of miR-146 targets involved in TLR signaling, IRAK1 and TRAF6, was assayed by qPCR in middle ear biopsies. Middle ear biopsies were cryosectioned and epithelial thickness measured by a certified pathologist. Proinflammatory cytokines induced expression of miR-146 in middle ear epithelial cells in vitro. Middle ear miR-146a and miR-146b expression was elevated in otitis media patients relative to control subjects and correlated with middle ear epithelial thickness. A trend towards inverse correlation was observed between miR-146 and TRAF6 expression in the clinical population. This report is the first to assess miRNA expression in a clinical population with OM. Findings herein suggest miR-146 may play a role in OM.