Soluble Wood Smoke Extract Promotes Barrier Dysfunction in Alveolar Epithelial Cells through a MAPK Signaling Pathway

Abstract

Wildfire smoke induces acute pulmonary distress and is of particular concern to risk groups such as the sick and elderly. Wood smoke (WS) contains many of the same toxic compounds as those found in cigarette smoke (CS) including polycyclic aromatic hydrocarbons, carbon monoxide, and free radicals. CS is a well-established risk factor for respiratory diseases such as asthma and COPD. Limited studies investigating the biological effects of WS on the airway epithelium have been performed. Using a cell culture-based model, we assessed the effects of a WS-infused solution on alveolar epithelial barrier function, cell migration, and survival. The average geometric mean of particles in the WS was 178 nm. GC/MS analysis of the WS solution identified phenolic and cellulosic compounds. WS exposure resulted in a significant reduction in barrier function, which peaked after 24 hours of continuous exposure. The junctional protein E-cadherin showed a prominent reduction in response to increasing concentrations of WS. Furthermore, WS significantly repressed cell migration following injury to the cell monolayer. There was no difference in cell viability following WS exposure. Mechanistically, WS exposure induced activation of the p44/42, but not p38, MAPK signaling pathway, and inhibition of p44/42 phosphorylation prevented the disruption of barrier function and loss of E-cadherin staining. Thus, WS may contribute to the breakdown of alveolar structure and function through a p44/42 MAPK-dependent pathway and may lead to the development and/or exacerbation of respiratory pathologies with chronic exposure.

Cardiovascular health impacts of wildfire smoke exposure

“…Similarly, after 40-h exposure to 40 μg/cm 2 of wood smoke extract, THP-1 cells entered S/G2 phase of the cell cycle, indicating decreased proliferation [ 23 ]. Studies have also shown evidence of cytotoxicity from exposure to wood smoke by using lactate dehydrogenase (LDH) release assay [ 57 , 58 , 100 , 106 ] or MTT assay [ 168 ], although the positive results were not present in all studies partly due to different wood type, cell line, and doses and exposure duration.…”

Effects of Air Pollutants on Airway Diseases

“…Wildfire smoke may induce acute pulmonary distress, particularly in high-risk groups such as the sick or elderly [ 142 ]. Wood smoke (WS) contains many of the toxic compounds found in CS, including polycyclic aromatic hydrocarbons, carbon monoxide, and free radicals.…”

“…Exposure to CS is a well-established risk factor for respiratory diseases such as asthma and COPD. WS may facilitate the breakdown of alveolar structure via a p44/42 MAPK-dependent pathway, and chronic WS exposure may exacerbate respiratory diseases [ 142 ].…”

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

“…The multifactorial aspect of solution generation results in a difficulty with standardizing protocols. To overcome this challenge, exhaustive detail regarding solution preparation is advisable and can be employed in conjunction with metrics such as optical density, mass spectroscopy, or chromatography (gas and liquid) [ 135 , 136 , 137 ]. Methods used to generate cigarette smoke extract can be found in Table 3 , while eCVE methods can be found in Table 4 .…”