The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats.
The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats.
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香烟烟雾暴露大鼠低温诱导粘液分泌过多的病理生理机制。
DOI：
10.3892/ijmm.2013.1535
复制
发表时间：
2014
影响因子：
5.4
通讯作者：
J. Perelman
中科院分区：
文献类型：
--
作者：
Min;Gang;Xiang;Sergey Tselluyko;J. Perelman
在最近的一项研究中，我们证明了瞬时受体电位melastatin 8（TRPM 8），一种由低温激活的钙渗透性阳离子通道，位于支气管上皮中，并在慢性阻塞性肺疾病受试者中上调，这导致他们对冷空气更敏感。在本研究中，我们发现，暴露于寒冷的温度诱导纤毛超微结构异常和上皮表面的粘液积累。将雄性Sprague-Dawley大鼠暴露于寒冷的温度下，以确定冷空气对纤毛和气道上皮表面超微结构变化的影响。还将大鼠暴露于香烟烟雾和/或低温，以确定烟雾和冷空气对TRPM 8表达的影响以及冷空气在香烟烟雾诱导的粘液分泌过多中的作用。实时荧光定量RT-PCR和蛋白质印迹分析后，我们观察到TRPM 8的mRNA和蛋白质在支气管组织香烟烟雾吸入后的高表达。如ELISA所示，与单独刺激（分别为冷空气和香烟烟雾）相比，同时吸入冷空气可提高粘蛋白5AC（MUC 5AC）蛋白水平以及香烟烟雾诱导的炎症因子[肿瘤坏死因子（TNF）-α和白细胞介素（IL）-8]水平。结果表明，冷空气刺激是负责支气管纤毛的超微结构异常，这有助于异常粘液清除。此外，冷空气通过香烟烟雾吸入引发的TRPM 8通道的表达升高，协同放大香烟烟雾诱导的粘液分泌过多和炎症因子的产生。
In a recent study, we demonstrated that transient receptor potential melastatin 8 (TRPM8), a calcium-permeable cation channel that is activated by cold temperatures, is localized in the bronchial epithelium and is upregulated in subjects with chronic obstructive pulmonary disease, which causes them to be more sensitive to cold air. In the present study, we found that exposure to cold temperatures induced ciliary ultrastructural anomalies and mucus accumulation on the epithelial surface. Male Sprague-Dawley rats were exposed to cold temperatures to determine the effects of cold air on ultrastructural changes in cilia and the airway epithelial surface. The rats were also exposed to cigarette smoke and/or cold temperatures to determine the effects of smoke and cold air on TRPM8 expression and the role of cold air in cigarette smoke-induced mucus hypersecretion. Following real-time RT-PCR and western blot analysis, we observed a high expression of TRPM8 mRNA and protein in the bronchial tissue following cigarette smoke inhalation. As shown by ELISA, concurrent cold air enhanced the levels of mucin 5AC (MUC5AC) protein, as well as those of inflammatory factors [tumor necrosis factor (TNF)-α and interleukin (IL)-8] that were induced by cigarette smoke inhalation to a greater extent than stimulation with separate stimuli (cold air and cigarette smoke separately). The results suggest that cold air stimuli are responsible for the ultrastructural abnormalities of bronchial cilia, which contribute to abnormal mucus clearance. In addition, cold air synergistically amplifies cigarette smoke-induced mucus hypersecretion and the production of inflammatory factors through the elevated expression of the TRPM8 channel that is initiated by cigarette smoke inhalation.
DOI：
10.1165/ajrcmb.24.2.4157
发表时间：
2001-02-01
影响因子：
6.4
作者：
Calderón-Garcidueñas, L;Valencia-Salazar, G;Carson, JL
通讯作者：
Carson, JL