Wood Smoke Disrupts Alveolar Epithelial Barrier Function through a p44/42 MAPK Signaling Pathway
Bibliographic record
Abstract
Background Wood smoke (WS) contains many of the same toxic compounds as those found in cigarette smoke (CS). Although CS is a leading cause of respiratory disease, limited studies investigating the mechanisms involved in WS mediated respiratory disease have been undertaken. Exposure to WS particulate reduces epithelial cell viability and barrier function. Both CS and WS induce MAPK signaling and contribute to airway remodeling. With an increase in the size, duration, and number of forest fires annually, there is a need for a better understanding with regards to the acute and chronic effects of WS on respiratory health. Therefore, we undertook studies to evaluate the role of WS exposure on the function and remodeling of the alveolar epithelium. Methods Birch wood was combusted and the smoke bubbled into PBS. The pH pf the resulting solution was adjusted to 7.1 and was considered 100% WS solution. Monolayers of A549 alveolar epithelial cells were exposed to increasing concentrations of WS for up to 48 hours. Cell viability was determined using MTT and trypan blue exclusion. Epithelial barrier function was monitored via electrical cell‐substrate impedance sensing (ECIS). Adhesion junctional structure was observed by immunofluorescent staining for E‐cadherin. Western blot was used to assess activation of MAPK signaling pathways. Results Concentrations of WS up to 10% had no effect on cell viability. WS promoted a concentration dependent reduction in epithelial barrier function after 24 hours which was maintained out to 48 hours. Cells not exposed to WS demonstrated distinct cobblestone E‐cadherin staining. Exposure to 2.5% WS diminished the cobblestone patterning after 24 hours and was completely lost after exposure to 5.0% WS. The wound healing capacity of cells after WS exposure was assessed using a scratch assay. After 48 hours, cells not exposed to WS had closed the scratched area by >50% whereas those cells exposed to 10% WS had closed the area by <20%. Exposure to WS induced phosphorylation of the p44/42, but not p38, MAPK signaling pathway. Pre‐treatment with the MAPK inhibitor U0126 prevented WS mediated epithelial barrier dysfunction. Additionally, U0126 preserved E‐cadherin cobblestone patterning even after WS exposure and had no effect on cell viability. Conclusions Exposure to WS disrupts alveolar epithelial adhesion that is partially regulated through the p44/42 MAPK signaling pathway. Pharmacological inhibition of p44/42 phosphorylation preserved epithelial barrier function, which may be as a result of maintained E‐cadherin‐mediated cell adhesion. Support or Funding Information Grant in aide funding was provided by provided CIHR (DJG). MRZ and CTT are recipients of CIHR Fellowships. MRZ also received a MSFHR Trainee Award. CC is a Canada Research Chair and holds the Astra‐Zeneca Chair in Occupational and Environmental Lung Disease at the University of British Columbia. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".