title: The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Min-Chao
authors.initials: MC
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Yang
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Zhou
authors.forename: Sergey
authors.initials: S
authors.lastname: Tselluyko
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003080:Cold Temperature / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D012907:Smoking / Q000009:adverse effects*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016209:Interleukin-8; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D014409:Tumor Necrosis Factor-alpha