Responses of human bronchial epithelial cells to ?-9- tetrahydrocannabinol exposure in vitro

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Megan Doldron (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Ramji Bhandari

Abstract: Cannabis sativa commonly known as Marijuana, is a well-known psychoactive drug that is frequently used in the United States (USA). Over 20 states have legalized marijuana for recreational or medical use, as such, understanding the impact of its use on human health becomes critical. Inhalation is a major route of exposure allowing substances to enter the body via the respiratory tract. Though smoke is typically exhaled right after being inhaled, its components are still interacting with the lining of the bronchus, specifically the bronchial epithelial cells. The effects of marijuana constituents on epithelial lining of the lungs are not fully understood. The objective of this study was to determine if ?-9-THC (?-9-tetrahydrocannabinol) exposure leads to adverse outcomes in the respiratory epithelium using normal human bronchial epithelial cell line (BEAS-2B) at the cellular and transcriptional levels. The results showed that ?-9-THC significantly decreased cell viability in 24 HRs 96 HRs, as well as in 9 days of culture. Transcriptome analysis of the ?-9-THC-exposed BEAS-2B cells revealed genes with distinctly altered patterns of expression, particularly those specific to ferroptosis, unfolded protein response, and tumor microenvironment pathways, suggesting effects of marijuana smoking on various biochemical pathways in the lung. The ?-9-THC induced cell death was ameliorated by the inhibition of the ferroptosis pathway, whereas the agonist of ferroptosis exacerbated the process of cell death, suggesting that ?-9-THC utilizes ferroptosis pathway to induce cell death in bronchial epithelial cells. Future studies are necessary to delineate other mechanisms predicted by transcriptome network analysis to understand the comprehensive picture of ?-9-THC-induced cell death and other adverse respiratory health outcomes in vitro and in vivo. [This abstract may have been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]

Additional Information

Publication
Dissertation
Language: English
Date: 2022
Keywords
Marijuana, THC, ?-9-tetrahydrocannabinol, ?-9-THC
Subjects
Pulmonary pharmacology
Tetrahydrocannabinol
Cannabis

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