1. Eucalyptus Wood Smoke Extract Elicits a Dose-Dependent Effect in Brain Endothelial Cells.
- Author
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You DJ, Gorman BM, Goshi N, Hum NR, Sebastian A, Kim YH, Enright HA, and Buchholz BA
- Subjects
- Humans, Cell Line, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Interleukin-8 metabolism, Interleukin-8 genetics, Dose-Response Relationship, Drug, NF-E2-Related Factor 2 metabolism, NF-E2-Related Factor 2 genetics, Wildfires, Smoke adverse effects, Endothelial Cells drug effects, Endothelial Cells metabolism, Eucalyptus chemistry, Wood chemistry, Brain metabolism, Brain drug effects, Plant Extracts pharmacology
- Abstract
The frequency, duration, and size of wildfires have been increasing, and the inhalation of wildfire smoke particles poses a significant risk to human health. Epidemiological studies have shown that wildfire smoke exposure is positively associated with cognitive and neurological dysfunctions. However, there is a significant gap in knowledge on how wildfire smoke exposure can affect the blood-brain barrier and cause molecular and cellular changes in the brain. Our study aims to determine the acute effect of smoldering eucalyptus wood smoke extract (WSE) on brain endothelial cells for potential neurotoxicity in vitro. Primary human brain microvascular endothelial cells (HBMEC) and immortalized human brain endothelial cell line (hCMEC/D3) were treated with different doses of WSE for 24 h. WSE treatment resulted in a dose-dependent increase in IL-8 in both HBMEC and hCMEC/D3. RNA-seq analyses showed a dose-dependent upregulation of genes involved in aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (NRF2) pathways and a decrease in tight junction markers in both HBMEC and hCMEC/D3. When comparing untreated controls, RNA-seq analyses showed that HBMEC have a higher expression of tight junction markers compared to hCMEC/D3. In summary, our study found that 24 h WSE treatment increases IL-8 production dose-dependently and decreases tight junction markers in both HBMEC and hCMEC/D3 that may be mediated through the AhR and NRF2 pathways, and HBMEC could be a better in vitro model for studying the effect of wood smoke extract or particles on brain endothelial cells.
- Published
- 2024
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