呼吸道合胞病毒诱导气道上皮粘液分泌及调节机制研究

目的探讨Toll样受体-4(TLR_4)和粘附分子-1(ICAM_1)在呼吸道合胞病毒(RSV)诱导气道上皮细胞粘液素表达中的作用。方法以气道上皮细胞NCI_H292为研究对象,体外培养并感染RSV,检测粘液素分泌和粘液素MAC5AC启动子的活性,研究阻断TLR_4和ICAM_1后对MAC5AC启动子活性的影响。结果NCI_H292细胞在感染RSV后,粘液分泌增加,MAC5AC启动子活性增强,与RSV数量和感染的时间呈正相关;MAC5AC启动子的激活依赖病毒的复制过程;在培养体系中预先加入抗TLR_4和ICAM_1中和抗体阻断TLR_4和ICMA_1不能抑制RSV诱导MAC5AC的活性。结论RSV可以诱导气道上皮细胞粘液素的表达,但不依赖TLR_4和ICAM_1分子的作用。

Mechanisms for RSV-induced mucin expression in bronchial epithelial cells

Objective Mucus hypersecretion is a common feature of respiratory syncytial virus (RSV)induced bronchiolitis. The mechanisms for RSV-induced mucin expression are poorly understood. This study was to explore the effects of Toll-like receptor-4 (TLR-4)and ICAM-1 on mucin expression in RSV infected epithelial cells. Methods Mucin secretion and mucin promoter gene activity were measured in RSV infected airway epithelial cell line NCI-H292 after blocking TLR-4 and ICAM-1 with specific antibodies. Results Mucin secretion and MUC5AC promoter activity increased in RSV infected NCI-H292 cells in time and dose dependent manner. Virus replication was essential for the expression of MUC5AC. Blocking of either TLR-4 or ICAM-1 with specific antibodies did not inhibit RSV induced MUC5AC expression. Conclusions These results suggest that RSV can induce mucin expression in epithelial cells,and the process is independent of both TLR-4 and ICAM-1.