Particulate matter induces airway epithelial barrier dysfunction in vivo and in vitro: from a more realistic inhalation scenario

Abstract

Particulate matter (PM) has become a major public health concern because of its adverse effects on health. The airway epithelial barrier is considered the primary position affected by inhaled particles, providing the first line to protect against environmental factors and constitutes chemical, physical and immunologic defenses. However, it still remains elusive what the influence of PM is towards the airway epithelial barrier, even in causing various diseases in a realistic inhalation scenario. In this study, C57BL/6 mice were exposed to PM_2.5 (3 mg kg⁻¹ b.w.) by oropharyngeal aspiration every other day for 4 weeks. The results exhibited significant histopathological damage and mucus barrier injury, as evidenced by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining, along with up-regulated MUC5AC and MUC5B mRNA levels in the lung. To imitate the inhalation of atmospheric PM deep into the respiratory system, mainly smaller particles as ultrafine particles (UFPs) coming into contact and interacting with the epithelial barrier, we further exposed human bronchial epithelial cells (BEAS-2B) to different concentrations of UFPs for 24 h. In response to UFPs, remarkable changes of epithelial permeability and decreased expression in several key biomarkers of tight junctions (TJs, i.e., ZO-1, occludin and claudin-2) and adherens junctions (AJs, i.e., E-cadherin and β-catenin) have been noted, which suggested an injured physical barrier. Interestingly, we further demonstrated that the addition of sodium butyrate, a short chain fatty acid (SCFA), strikingly antagonized the UFP-induced cytotoxicity and impaired epithelium barrier function. Additionally, the underlying mechanism is associated with MAPK signaling pathway activation. These in vitro and in vivo findings practically indicated ambient particulate exposure induced airway epithelial barrier dysfunction, which provided a strong theoretical basis for the health risk evaluation of particulate pollution.