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

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.

Effect of concentration and duration of particulate matter exposure on the transcriptome and DNA methylome of bronchial epithelial cells

“…PM 2.5 was isolated from ambient air pollution collected in Beijing, China from 19–21 January 2015 as previously described ( 20 ). Low volume manual samplers placed on the rooftop of Peking University School of Public Health collected PM 2.5 over a 24-h period on 90 mm Emfab filters, which are made of borosilicate fibers reinforced with woven cloth and bonded with polytetrafluoroethylene (TX40HI20WW, part #7234, Pall Company, Beijing Office, Beijing, China).…”

“…These studies have shown that epithelial cells under these conditions persistently release inflammatory cytokines, develop epigenetic changes, and undergo epithelial–mesenchymal transition ( 17–19 ). Our laboratory has shown that repeated exposure to low-concentrations of PM 2.5 over seven days resulted in the upregulation of many genes that were not observed after a single exposure to PM 2.5 ( 20 ). However, a full transcriptomic analysis of this treatment protocol—along with a comparison with higher concentrations and short-term exposure—has not been reported.…”

Hydrogen Sulfide Attenuates Particulate Matter-Induced Emphysema and Airway Inflammation Through Nrf2-Dependent Manner

“…As previously described, a high volume air sampler with a pump flow rate of 1.13 m 3 /min was placed on the rooftop of the School of Public Health Building of Peking University in Beijing, China to collect PM 2.5 . The daily PM 2.5 samples were collected on 90 mm Emfab filters (TX40HI20WW, part #7234, Pall Company, Beijing Office, Beijing, China) (Tripathi et al, 2018). To extract PM 2.5 , the filters were cut up into small pieces and placed in 90 ml sterile ultrapure water, then sonicated for total 2 h with every 20 min gently shaking the beaker at constant temperature.…”

The Aryl Hydrocarbon Receptor in Asthma: Friend or Foe?

“…Airway epithelial cells are able to modulate allergic airway inflammation by their ability to produce a variety of inflammatory mediators including the alarmins IL-33, IL-25 and TSLP, critical for driving type 2 inflammation in the lung tissue. In the human bronchial epithelial cell line BEAS2B, TSLP expression is induced by particle matter (PM) with a diameter <2.5 µm (PM 2.5 ) in an AhR-dependent pathway [ 93 ]. These data are in agreement with the ability of AhR to bind alarmin promoters and activate their transcription [ 30 ].…”