Eucalyptus Wood Smoke Extract Elicits a Dose-Dependent Effect in Brain Endothelial Cells

You, Dorothy J.; Gorman, Bria M.; Goshi, Noah; Hum, Nicholas R.; Sebastian, Aimy; Kim, Yong Ho; Enright, Heather A.; Buchholz, Bruce A.

doi:10.3390/ijms251910288

Title: Eucalyptus Wood Smoke Extract Elicits a Dose-Dependent Effect in Brain Endothelial Cells

Journal Article · 24 September 2024 · International Journal of Molecular Sciences (Online)

DOI: https://doi.org/10.3390/ijms251910288 · OSTI ID:2476471

You, Dorothy J. ^[1];

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^[2];

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Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

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.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 2476471

Report Number(s):: LLNL--JRNL-866898; 1101896

Journal Information:: International Journal of Molecular Sciences (Online), Journal Name: International Journal of Molecular Sciences (Online) Journal Issue: 19 Vol. 25; ISSN 1422-0067

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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Transcriptional Profiling of Human Brain Endothelial Cells Reveals Key Properties Crucial for Predictive In Vitro Blood-Brain Barrier Models Urich, Eduard; Lazic, Stanley E.; Molnos, Juliette PLoS ONE, Vol. 7, Issue 5 https://doi.org/10.1371/journal.pone.0038149	journal	May 2012
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Oxidative Damage and Antioxidant Defense in Ferroptosis Kuang, Feimei; Liu, Jiao; Tang, Daolin Frontiers in Cell and Developmental Biology, Vol. 8 https://doi.org/10.3389/fcell.2020.586578	journal	September 2020
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype Kumari, Ruchi; Jat, Parmjit Frontiers in Cell and Developmental Biology, Vol. 9 https://doi.org/10.3389/fcell.2021.645593	journal	March 2021
Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy? Qiu, Yan-mei; Zhang, Chun-lin; Chen, An-qi Frontiers in Immunology, Vol. 12 https://doi.org/10.3389/fimmu.2021.678744	journal	June 2021
Cellular Senescence in Neurodegenerative Diseases Martínez-Cué, Carmen; Rueda, Noemí Frontiers in Cellular Neuroscience, Vol. 14 https://doi.org/10.3389/fncel.2020.00016	journal	February 2020
Hippocampal but Not Serum Cytokine Levels Are Altered by Traffic-Related Air Pollution in TgF344-AD and Wildtype Fischer 344 Rats in a Sex- and Age-Dependent Manner Patten, Kelley T.; Valenzuela, Anthony E.; Wallis, Christopher Frontiers in Cellular Neuroscience, Vol. 16 https://doi.org/10.3389/fncel.2022.861733	journal	April 2022
A review of respirable fine particulate matter (PM2.5)-induced brain damage Li, Wei; Lin, Guohui; Xiao, Zaixing Frontiers in Molecular Neuroscience, Vol. 15 https://doi.org/10.3389/fnmol.2022.967174	journal	September 2022
The Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Psychiatric Disorders Müller, Norbert Frontiers in Pharmacology, Vol. 10 https://doi.org/10.3389/fphar.2019.01251	journal	November 2019
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The Aryl Hydrocarbon Receptor Suppresses Chronic Smoke-Induced Pulmonary Inflammation Guerrina, Necola; Traboulsi, Hussein; Eidelman, David H. Frontiers in Toxicology, Vol. 3 https://doi.org/10.3389/ftox.2021.653569	journal	July 2021
Aryl Hydrocarbon Receptor Signaling Synergizes with TLR/NF-κB-Signaling for Induction of IL-22 Through Canonical and Non-Canonical AhR Pathways Ishihara, Yasuhiro; Kado, Sarah Y.; Bein, Keith J. Frontiers in Toxicology, Vol. 3 https://doi.org/10.3389/ftox.2021.787360	journal	February 2022
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Pathophysiological Impact of Cigarette Smoke Exposure on the Cerebrovascular System with a Focus on the Blood-brain Barrier: Expanding the Awareness of Smoking Toxicity in an Underappreciated Area Mazzone, Peter; Tierney, William; Hossain, Mohammed International Journal of Environmental Research and Public Health, Vol. 7, Issue 12 https://doi.org/10.3390/ijerph7124111	journal	November 2010
Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance Grishanova, Alevtina Y.; Perepechaeva, Maria L. International Journal of Molecular Sciences, Vol. 23, Issue 12 https://doi.org/10.3390/ijms23126719	journal	June 2022

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