Elevated expression of miR-146 involved in regulating mice pulmonary dysfunction after exposure to PM2.5.

Abstract

Exposure to atmospheric fine particulate matter has short-term and long-term adverse effects on pulmonary function, especially PM2.5; however, early lung function impairment is not easily detected in time. Notably, microRNAs (miRNAs) have been classified as novel biomarkers for diseases related to PM. Thus, the purpose of this study was to investigate whether miR-146 was related to the decline of lung function after exposure to air pollution. Thirty BALB/c mice were subjected to different concentrations of PM2.5 by noninvasive tracheal instillation for 56 days (two times one week), after which we detected the histopathological changes of mice lung, pulmonary functions, pro-inflammatory factors levels in bronchoalveolar lavage fluid (BALF) and lung tissue homogenate, and the relative expression of microRNA-146a and -146b. When BALB/c mice were exposed to 10 mg/kg PM2.5, severe changes such as widened alveolar interval and diffuse infiltration of macrophages with engulfed PM2.5 particles (dust cells) were found. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) were decreased significantly. Expiratory resistance (Re) and inspiratory resistance (Ri) were increased significantly in the 5 mg/kg and 10 mg/kg PM2.5 groups, meanwhile lung resistance increased and MVV (maximum minute ventilation) decreased from the general tendency; however, pro-inflammatory factors interleukin-6 (IL-6), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were increased dramatically. MiR-146a and miR-146b were elevated remarkably in the PM2.5 groups compared to the NS group. We also found miR-146 had negative relationships with PIF and PEF, especially miR-146b. Thus, elevated miR-146a and miR-146b may have a relationship with pulmonary dysfunction after PM2.5 chronic exposure.