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Transcriptomic Response of Primary Human Bronchial Cells to Repeated Exposures of Cigarette and ENDS Preparations

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Abstract

Cigarette smoke deregulates several biological pathways by modulating gene expression in airway epithelial cells and altering the physiology of the airway epithelium. The effects of repeated exposures of electronic cigarette delivery systems (ENDS) on gene expression in airway epithelium are relatively unknown. In order to assess the effect of repeated exposures of ENDS, primary normal human bronchial epithelial (NHBE) cells grown at air-liquid interface (ALI) were exposed to cigarette and ENDS preparations daily for 10 days. Cigarette smoke preparations significantly altered gene expression in a dose-dependent manner compared to vehicle control, including genes linked to oxidative stress, xenobiotic metabolism, cancer pathways, epithelial-mesenchymal transition, fatty acid metabolism, degradation of collagen and extracellular matrix, O-glycosylation, and chemokines/cytokines, which are known pathways found to be altered in smokers. Conversely, ENDS preparations had minimal effect on transcriptional pathways. This study revealed that a sub-chronic exposure of primary NHBE cultures to cigarette and ENDS preparations differentially regulated genes and canonical pathways, with minimal effect observed with ENDS preparations compared to cigarette preparations. This study also demonstrates the versatility of primary NHBE cultures at ALI to evaluate repeat-dose exposures of tobacco products.

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Acknowledgements

This work was in part funded by RAI Services Company under a collaborative research agreement with the Ohio State University. We would like to acknowledge the assistance of the Genomics Core at The Ohio State University which was supported by NIH grant P30 CA016058.

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Author notes

  1. G. L. Prasad

    Present address: Prior employee of RAI Services Company, Winston-Salem, NC, USA

Authors and Affiliations

  1. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA

    Rachael E. Rayner, Jack Wellmerling & Estelle Cormet-Boyaka

  2. RAI Services Company, Winston Salem, NC, 27102, USA

    Patrudu Makena

  3. Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA

    Jing Zhao

  4. Prasad Scientific Consulting LLC, Lewisville, NC, USA

    G. L. Prasad

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  1. Rachael E. Rayner
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Contributions

R.E.R. designed the study, completed experiments, analyzed the data, drafted, and edited the manuscript. J.W. helped complete experiments and edited the manuscript. J.Z. analyzed the transcriptomics data and edited the manuscript. P.M. designed the study and edited the manuscript. G.L.P. reviewed and edited the manuscript. E.C.-B. designed the study, analyzed the data, and edited the manuscript.

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Correspondence to Estelle Cormet-Boyaka.

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Conflict of interest

P.M. and G.L.P. are employees of RAI Services Company. RAI Services Company is a wholly-owned subsidiary of Reynolds American, Inc. which is a wholly-owned subsidiary of British American Tobacco plc. R.E.R., J.W., J.Z., and E.C.B. declare that they have no competing financial interests.

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Rayner, R.E., Wellmerling, J., Makena, P. et al. Transcriptomic Response of Primary Human Bronchial Cells to Repeated Exposures of Cigarette and ENDS Preparations. Cell Biochem Biophys 80, 217–228 (2022). https://doi.org/10.1007/s12013-021-01042-4

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