Smirnova M G, Birchall J P, Pearson J P
Department of Physiological Sciences, Medical School, University of Newcastle, Newcastle upon Tyne, UK.
Cytokine. 2000 Nov;12(11):1732-6. doi: 10.1006/cyto.2000.0763.
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-HGM-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.
肿瘤坏死因子-α（TNF-α）被认为与分泌性中耳炎（OME）的病因有关，在OME中，杯状细胞在改良的呼吸道上皮中增殖，导致富含粘蛋白的积液在中耳裂中积聚。MUC5AC粘蛋白基因产物已被确定为这些积液的一个组成部分。在此，我们使用分泌MUC5AC粘蛋白的HT29-MTX杯状细胞系作为模型来研究TNF-α对杯状细胞的影响。用单克隆抗体NCL-HGM-45M1鉴定和定量MUC5AC粘蛋白。TNF-α以剂量依赖的方式刺激MUC5AC粘蛋白分泌，20 ng/ml产生最大刺激。汇合前和汇合后的细胞在7小时后均显示出峰值刺激，但汇合前的细胞粘蛋白分泌过多水平是其两倍。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。这种粘蛋白分泌过多随后可能导致粘液纤毛清除系统失效，导致富含粘蛋白的积液在中耳积聚，并使疾病发展到更慢性的阶段。
