Variation in doses and duration of particulate matter exposure in bronchial epithelial cells results in upregulation of different genes associated with airway disorders

Toxicol In Vitro. 2018 Sep;51:95-105. doi: 10.1016/j.tiv.2018.05.004. Epub 2018 May 9.

Abstract

Exposure to particulate matter < 2.5 μm (PM2.5) is associated with a variety of airway diseases. Although studies have demonstrated that high doses of PM2.5 cause cytotoxicity and changes to gene expression in bronchial epithelial cells, the effect of lower doses and repeated exposure to PM2.5 are less well studied. Here, we treated BEAS-2B cells with varying doses of PM2.5 for 1-7 days and examined the expression of a variety of genes implicated in airway disorders. At high doses, PM2.5 increased the expression of IL6, TNF, TSLP, CSF2, PTGS2, IL4R, and SPINK5. Other genes such as ADAM33, ORMDL3, DPP10 and CYP1A1, however, were increased by PM2.5 at much lower doses (≤1 μg/cm2). Repeated exposure to PM2.5 at 1 or 5 μg/cm2 every day for 7 days increased the sensitivity and magnitude of change for all of the aforementioned genes. Genes such as IL13 and TGFB1, increased only when cells were repeatedly exposed to PM2.5. Treatment with an antioxidant, or inhibitors to aryl hydrocarbon receptor or NF-κB attenuated the effect of PM2.5. These data demonstrate that PM2.5 exerts pleiotropic actions that differ by dose and duration that affect a variety of genes important to the development of airway disease.

Keywords: Aryl hydrocarbon receptor (AhR); BEAS-2B; Nuclear factor κB (NF-κB); PM(2.5); Reactive oxygen species (ROS).

MeSH terms

  • Air Pollutants / toxicity*
  • Bronchi / cytology
  • Cell Line
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Particulate Matter / toxicity*
  • Respiratory Tract Diseases / genetics

Substances

  • Air Pollutants
  • Particulate Matter