Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8

Title: [Mechanisms of mucus hypersecretion in airway of rats induced by synergies between cold air and cigarette smoke inhalation and intervention effects of drugs].

Authors: Min-Chao Li, Juliy M Perelman, Victor P Kolosov, Xiang-Dong Zhou

Journal, date & volume: Zhonghua Yi Xue Za Zhi, 2012 Aug 28 , 92, 2283-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23158492

Abstract
To explore the mechanisms of mucus hypersecretion in airway of rats induced by the synergies between cold air and cigarette smoke inhalation and understand the intervention effects of saussurea and budesonide in this process.A total of 70 SD rats were randomly divided into 7 groups. Group A: control; Group B: cold stimulation group receiving cold air inhalation for 3 h daily for 40 d; Group C: cigarette smoke inhalation group receiving cigarette smoke inhalation for 0.5 h daily for 40 d; Group D: cigarette smoke inhalation + cold stimulation group; Group E: cigarette smoke inhalation + cold stimulation + saussurea (0.8 mg/kg saussurea intraperitoneally injected once daily for 40 d); Group F: cigarette smoke inhalation + cold stimulation + inhaled budesonide (0.5 mg/kg inhaled once daily for 40 d); Group G: cigarette smoke inhalation + cold stimulation + saussurea + inhaled budesonide. The relative quantities of TRPM8 mRNA within bronchial epithelium of each group were detected by real-time polymerase chain reaction (PCR) and TRPM8 protein was detected by immunohistochemical assay and Western blot. The levels of mucin (MUC) 5AC, interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay.TRPM8 mRNA of groups A-G were 1.00 ± 0.00, 0.98 ± 0.07, 2.27 ± 0.29, 2.31 ± 0.30, 1.55 ± 0.38, 1.66 ± 0.40 and 1.31 ± 0.23; TRPM8 protein 0.16 ± 0.05, 0.16 ± 0.04, 0.22 ± 0.06, 0.25 ± 0.05, 0.17 ± 0.04, 0.18 ± 0.03, 0.15 ± 0.05, 0.25 ± 0.04, 0.24 ± 0.03, 0.58 ± 0.06, 0.56 ± 0.09, 0.41 ± 0.09, 0.39 ± 0.07 and 0.20 ± 0.06 respectively. TRPM8 mRNA and protein of groups C and D were significantly higher than those of group A. And groups E, F and G were significantly lower than those of group D (all P < 0.05). In BALF of groups A-G, MUC5AC were (57 ± 6), (69 ± 5), (66 ± 4), (185 ± 43), (142 ± 30), (147 ± 36) and (60 ± 11) µg/mg, IL-8 (58 ± 14), (146 ± 38), (134 ± 29), (379 ± 101), (262 ± 67), (294 ± 70) and (81 ± 27) ng/L, TNF-α(153 ± 28), (208 ± 90), (274 ± 64), (600 ± 113), (458 ± 96), (498 ± 84) and (169 ± 65) ng/L respectively. The values of groups B, C and D were significantly higher than those of group A (all P < 0.05) while groups E, F and G were significantly lower than those of group D (all P < 0.05). Cigarette smoke inhalation and cold stimulation synergistically enhanced the expression of MUC5AC, IL-8 and TNF-α. Saussurea and inhaled budesonide synergistically inhibited the expression of MUC5AC, IL-8 and TNF-α.Cold air inhalation evokes the release of proinflammatory cytokines and MUC5AC via activated TRPM8 channel up-regulated by cigarette smoke inhalation. Saussurea and inhaled budesonide synergistically inhibits the above mentioned process.