A recent study published in the American Journal of Respiratory and Critical Care Medicine found that sub-cytotoxic benzene exposure can disrupt oxidative stress signaling and immune cell chemotaxis in airway epithelial cells without activating typical inflammatory of metabolic pathways. Read about these new findings and their implications for respiratory disease development, which were presented at the American Thoracic Society 2025 International Conference.
The Subtle Threats of Benzene on Airway Health: Insights from an In Vitro ALI Model
05/29/2025
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Researchers at Texas A&M University recently explored how benzene, a common volatile organic compound (VOC), may contribute to mechanisms relevant to respiratory disease development (RDD). Although benzene’s association with respiratory and systemic health outcomes is well documented, this study aimed to examine specific molecular responses within bronchial epithelial cells, a key cell type in airway barrier function and immune signaling.
The Experimental Model
The investigators used an in vitro air-liquid interface (ALI) culture system of 16HBE bronchial epithelial cells to simulate real-world respiratory exposure. Cells were exposed to benzene at concentrations representing both environmental and occupational levels (10, 100, 1,000, and 10,000 parts per billion).
The aim was to assess sub-cytotoxic responses in oxidative stress signaling and inflammatory gene expression as well as the ability of exposed cells to influence immune cell behavior.
Observed Molecular and Functional Changes
Following exposure, several patterns emerged:
- Oxidative Stress Response: Gene expression of heme oxygenase-1 (HMOX-1), a marker of oxidative stress response, increased across exposure levels, indicating a possible early stress signal.
- Chemokine Receptor Upregulation: Expression levels of chemokine receptors CCR3, CXCR3, and CX3CR1 were elevated, which may suggest altered immune cell signaling or recruitment potential.
- Cytokine Expression: Gene expression for pro-inflammatory cytokines including IL-6, IL-8, IL-13, and TNF-α was reduced following benzene exposure. Despite this, neutrophils showed directed migration toward conditioned medium from exposed epithelial cells, indicating that epithelial chemotactic signaling was promoted.
- CYP2E1 Expression: There were no significant changes in expression of cytochrome P450-2E1 (CYP2E1), a known metabolic mediator of benzene toxicity, suggesting the observed effects may arise independently of classical metabolic activation pathways.
The evidence suggests that sub-cytotoxic benzene exposure can influence oxidative stress pathways and chemotactic signaling in airway epithelial cells without eliciting classical inflammatory cytokine responses or CYP2E1 upregulation.
These findings may provide a useful basis for further investigation into how inhaled pollutants affect early molecular events relevant to RDD. The ALI model may serve as a valuable platform for exploring epithelial-immune interactions in response to airborne toxicants.
Reference
Vitucci E, Cannon CL, and Johnson N. ALI benzene exposure induces oxidative stress in the bronchial epithelium and promotes immune cell chemotaxis in vitro [abstract]. Am J Respir Crit Care Med 2025;211:A5109. https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A5109
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