Wood smoke (WS) exposure is associated with increased prevalence of chronic bronchitis and rapid decline in lung function. However, potency of WS and cigarette smoke (CS) in activating mucin gene expression has not been compared.
Yohannes Tesfaigzi1 and Elias Awji1
1COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NMUnited States
Introduction: Wood smoke (WS) exposure is associated with increased prevalence of chronic bronchitis and rapid decline in lung function. However, potency of WS and cigarette smoke (CS) in activating mucin gene expression has not been compared.
Aims and objectives: We tested the hypothesis that WS is more potent than CS in causing mucous cell metaplasia (MCM).
Methods: C57BL/6 mice were exposed for 30 d to filtered air (FA) or CS for 5 days/week and 6 hours/day at 250 mg/m3 total particulate matter (TPM) or to WS for 2 h/d at 10 mg TPM/m3. Extent of MCM was determined in stained lung sections. Mucin gene expression was analyzed by Western blot, qRT-PCR, and immunofluorescent staining. Findings were replicated in differentiated primary airway epithelial cultures from human (HAEC) and murine cells (MAECs).
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Results: WS exposure at 25-fold lower TPM concentrations than CS increased Muc5ac, Muc5b, SPDEF and Bcl-2 mRNAs in the lungs of mice, while these mRNAs were not significantly increased by FA or CS. This increase was accompanied with a 2-fold increase in MCM by WS compared with CS. Combined exposure to CS and WS showed MCM similar to WS alone. In HAEC, WS at 40-fold lower concentration increased levels of Muc5ac, Muc5b, SPDEF and Bcl-2 mRNAs by 2.5-fold more than CS. Further, WS compared with CS showed significantly enhanced activation of ERK1/2 and p53. Inhibition of ERK1/2 with UO126 suppressed WS-induced MUC5B but not MUC5AC mRNA levels, and WS-induced MUC5AC and SPDEF mRNA levels were reduced in p53-/- compared to p53+/+ MAECs.
Conclusions: Exposure to WS compared to CS causes increased MCM by activating the ERK1/2 and p53 pathways to increase MUC5B and MUC5AC expression, respectively.