Abstract
Exposure to wildfire smoke particulate matter (PM) is increasing around the world due to unprecedented wildfires. Numerous adverse health effects are associated with wildfire smoke PM exposures, including an increased risk of developing lung cancer in wildland firefighters. However more research is needed to fully comprehend the mechanisms involved in response to these exposures. We specifically focused on determining the effects of Douglas fir wood smoke particles (WSP) on several critical cellular events, also known to be included as hallmarks of cancer, on a bronchial epithelial cell line (BEAS-2B). The endpoints studied were pro-inflammatory cytokines/bioactive lipids and dysregulation of gap junctional intercellular communication at noncytotoxic concentrations of WSP. Polycyclic aromatic hydrocarbons (PAHs) were identified in WSP using gas chromatography-mass spectrometry (GC/MS), and WSP increased the mRNA levels of the PAH metabolizing enzymes CYP1A1 and CYP1B1. Levels of mRNA expression of the pro- inflammatory markers TNF, IL-6, COX-2, and IL-8, were significantly elevated above the control vehicle at 5 μg/mL WSP. IL-6 secretion was also significantly increased above the control vehicle at 5 μg/mL WSP. Additionally, there was a significant decrease in the expression of gap junction genes (GJA1 and GJB2) along with decreased activity of gap junctional intercellular communication in response to 5 μg/mL WSP. Parthenolide, a strong pan-anti-inflammatory and anti-cancer compound, prevented WSP-induced dysregulation of gap junction activity and TNF mRNA expression. Lastly, epiregulin, a known growth factor upregulated in premalignant stages of lung cancer specifically during tumor-promoting inflammation, was also significantly elevated above control in response to 5 μg/mL WSP. These early results support a link between inflammation and gap junctions and provide a critical new mechanistic understanding of how WSP contribute to early adverse events in a lung cell line along with the potential to prevent these adverse outcomes with interventions such as parthenolide.