TNF-alpha in the regulation of MUC5AC secretion: Some aspects of cytokine-induced mucin hypersecretion on the in vitro model
TNF-alpha in the regulation of MUC5AC secretion: Some aspects of cytokine-induced mucin hypersecretion on the in vitro model
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DOI：
10.1006/cyto.2000.0763
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发表时间：
2000-11-01
期刊：
影响因子：
3.8
通讯作者：
Pearson, JP
中科院分区：
文献类型：
--
作者：
Smirnova, MG;Birchall, JP;Pearson, JP
TNF-α与渗出性中耳炎（OME）的病因有关，其中杯状细胞在修饰的呼吸上皮中增殖，导致富含粘蛋白的渗出物在中耳裂中积聚。MUC 5AC粘蛋白基因产物已被鉴定为这些渗出液的组分。在此，我们使用分泌MUC 5AC粘蛋白的HT 29-MTX杯状细胞系作为模型来研究TNF-α对杯状细胞的作用。用单克隆抗体NCL-NGM-45 M1鉴定和定量MUC 5AC粘蛋白。TNF-α以剂量依赖性方式刺激MUC 5AC粘蛋白分泌，20 ng/ml产生最大刺激。融合前和融合细胞均在7 h后显示峰值刺激，然而融合前细胞显示粘蛋白高分泌水平的两倍。这些结果表明，TNF-α刺激粘蛋白分泌可能在OME发展的早期急性期起重要作用，这种粘蛋白的分泌过多然后可能导致粘膜纤毛清除系统的失败，导致富含粘蛋白的渗出物在中耳中的积累和向疾病的更慢性阶段的移动。(C)北京大学出版社.
Tnf-alpha has been implicated in the aetiology of otitis media with effusion (OME), where goblet cells proliferate in a modified respiratory epithelium, leading to the accumulation of a mucin-rich effusion in the middle-ear cleft. The MUC5AC mucin gene product has been identified as a component of these effusions, Here we have used the HT29-MTX goblet cell line, which secretes MUC5AC mucin, as a model to study the effect of TNF-alpha on goblet cells. MUC5AC mucin was identified and quantitated with a monoclonal antibody NCL-NGM-45M1. TNF-alpha stimulates MUC5AC mucin secretion in a dose-dependent manner, with 20 ng/ml producing maximal stimulation, Both pre-confluent and confluent cells showed peak stimulation after 7 h, however the pre-confluent cells showed twice the level of mucin hypersecretion, These results suggest that TNF-alpha stimulation of mucin secretion could play an important role in the early acute phase of the development of OME, This hypersecretion of mucin could then lead to the failure of the mucociliary clearance system, resulting in the accumulation of a mucin-rich effusion in the middle ear and the movement to a more chronic phase of the disease. (C) 2000 Academic Press.