人中耳上皮模型中细胞因子对黏蛋白分泌的调节
Cytokine regulation of mucin secretion in a human middle ear epithelial model.
作者信息
Samuel Erica A, Burrows Amy, Kerschner Joseph E
机构信息
Division of Pediatric Otolaryngology, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, 9000 W. Wisconsin Avenue, Milwaukee, WI 53226, USA.
出版信息
Cytokine. 2008 Jan;41(1):38-43. doi: 10.1016/j.cyto.2007.10.009. Epub 2007 Dec 11.
OBJECTIVES
Middle ear mucins are associated with otitis media (OM), contribute to hearing loss and are regulated by cytokines. This work investigates the regulation of mucin secretion from human middle ear epithelial cells (HMEEC) by inflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and cytokine inhibitors interleukin-1 receptor antagonist (IL-1ra) and anti-tumor necrosis factor-alpha antibody (TNFab).
METHODS
HMEEC were exposed to IL-1beta and TNF-alpha in a dose- and time-dependent manner. Cytokine stimulated HMEEC were also exposed to IL-1ra and TNFab in a dose-dependent manner. Mucin secretion was characterized by exclusion chromatography and liquid scintillation.
RESULTS
HMEEC exposed to IL-1beta and TNF-alpha demonstrated significant upregulation of mucin secretion in a dose-dependent fashion. Cultures exposed to IL-1beta at 100ng/ml and TNF-alpha at 200ng/ml showed increased mucin secretion in time-dependent experiments at 16h (P=0.00008) for TNF-alpha and 8 (P=0.028) and 16h (P=0.00001) for IL-1beta. IL-1ra and TNFab inhibited the effects of increased mucin secretion by IL-1beta and TNF-alpha.
CONCLUSIONS
IL-1beta and TNF-alpha upregulate mucin secretion from HMEEC in a dose- and time-dependant manner and these effects can be inhibited by cytokine blockade. Improved understanding of these mechanisms has the potential to alter the approach and management of OM and lead to novel therapeutic interventions.
目的
中耳黏蛋白与中耳炎（OM）相关，会导致听力损失且受细胞因子调节。本研究调查炎性细胞因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）以及细胞因子抑制剂白细胞介素-1受体拮抗剂（IL-1ra）和抗肿瘤坏死因子-α抗体（TNFab）对人中耳上皮细胞（HMEEC）黏蛋白分泌的调节作用。
方法
以剂量和时间依赖性方式将HMEEC暴露于IL-1β和TNF-α。细胞因子刺激的HMEEC也以剂量依赖性方式暴露于IL-1ra和TNFab。通过排阻色谱法和液体闪烁法对黏蛋白分泌进行表征。
结果
暴露于IL-1β和TNF-α的HMEEC显示黏蛋白分泌以剂量依赖性方式显著上调。在时间依赖性实验中，暴露于100ng/ml IL-1β和200ng/ml TNF-α的培养物在16小时时TNF-α组黏蛋白分泌增加（P = 0.00008），IL-1β组在8小时（P = 0.028）和16小时（P = 0.00001）时黏蛋白分泌增加。IL-1ra和TNFab抑制IL-1β和TNF-α增加黏蛋白分泌的作用。
结论
IL-1β和TNF-α以剂量和时间依赖性方式上调HMEEC的黏蛋白分泌，这些作用可通过细胞因子阻断来抑制。对这些机制的深入了解有可能改变OM的治疗方法和管理方式，并带来新的治疗干预措施。
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