RNA Sequencing Reveals Inflammatory and Metabolic Changes in the Lung and Brain After Carbon Black and Naphthalene Whole Body Inhalation Exposure in a Rodent Model of Military Burn Pit Exposures

Authors

Allison M. Haaning
Brian J. Sandri
Henry L. Wyneken
William T. Goldsmith
Joshua P. Nixon
Timothy R. Nurkiewicz
Chris H. Wendt
Paul Barach, Thomas Jefferson UniversityFollow
Janeen H. Trembley
Tammy A. Butterick

Document Type

Article

Publication Date

7-26-2025

Comments

This article is the author’s final published version in International Journal of Molecular Sciences, Volume 26, Issue 15, 2025, Article number 7238.

The published version is available at https://doi.org/10.3390/ijms26157238. Copyright © 2025 by the authors.

Abstract

Military personnel deployed to Iraq and Afghanistan were exposed to emissions from open-air burn pits, where plastics, metals, and medical waste were incinerated. These exposures have been linked to deployment-related respiratory diseases (DRRD) and may also impact neurological health via the lung-brain axis. To investigate molecular mechanisms, adult male rats were exposed to filtered air, naphthalene (a representative volatile organic compound), or a combination of naphthalene and carbon black (surrogate for particulate matter; CBN) via whole-body inhalation (six hours/day, three consecutive days). Lung, brain, and plasma samples were collected 24 h after the final exposure. Pro-inflammatory biomarkers were assessed using multiplex electrochemiluminescence and western blot. Differentially expressed genes (DEGs) were identified by RNA sequencing, and elastic net modeling was used to define exposure-predictive gene signatures. CBN exposure altered inflammatory biomarkers across tissues, with activation of nuclear factor kappa B (NF-κB) signaling. In the lung, gene set enrichment revealed activated pathways related to proliferation and inflammation, while epithelial-mesenchymal transition (EMT) and oxidative phosphorylation were suppressed. In the brain, EMT, inflammation, and senescence pathways were activated, while ribosomal function and oxidative metabolism were downregulated. Elastic net modeling identified a lung gene signature predictive of CBN exposure, including Kcnq3, Tgfbr1, and Tm4sf19. These findings demonstrate that inhalation of a surrogate burn pit mixture induces inflammatory and metabolic gene expression changes in both lung and brain tissues, supporting the utility of this animal model for understanding systemic effects of airborne military toxicants and for identifying potential biomarkers relevant to DRRD and Veteran health.

Recommended Citation

Haaning, Allison M.; Sandri, Brian J.; Wyneken, Henry L.; Goldsmith, William T.; Nixon, Joshua P.; Nurkiewicz, Timothy R.; Wendt, Chris H.; Barach, Paul; Trembley, Janeen H.; and Butterick, Tammy A., "RNA Sequencing Reveals Inflammatory and Metabolic Changes in the Lung and Brain After Carbon Black and Naphthalene Whole Body Inhalation Exposure in a Rodent Model of Military Burn Pit Exposures" (2025). College of Population Health Faculty Papers. Paper 226.
https://jdc.jefferson.edu/healthpolicyfaculty/226

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English