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Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa

Van Der Does AM, Mahbub RM, Ninaber DK, Rathnayake SNH, Timens W, Van Den Berge M, Aliee H, Theis FJ, Nawijn MC, Hiemstra PS, Faiz A (2022)

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Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 23

Article Number: 227

Journal Issue: 1

DOI: 10.1186/s12931-022-02150-2

Abstract

Background: Despite the well-known detrimental effects of cigarette smoke (CS), little is known about the complex gene expression dynamics in the early stages after exposure. This study aims to investigate early transcriptomic responses following CS exposure of airway epithelial cells in culture and compare these to those found in human CS exposure studies. Methods: Primary bronchial epithelial cells (PBEC) were differentiated at the air–liquid interface (ALI) and exposed to whole CS. Bulk RNA-sequencing was performed at 1 h, 4 h, and 24 h hereafter, followed by differential gene expression analysis. Results were additionally compared to data retrieved from human CS studies. Results: ALI-PBEC gene expression in response to CS was most significantly changed at 4 h after exposure. Early transcriptomic changes (1 h, 4 h post CS exposure) were related to oxidative stress, xenobiotic metabolism, higher expression of immediate early genes and pro-inflammatory pathways (i.e., Nrf2, AP-1, AhR). At 24 h, ferroptosis-associated genes were significantly increased, whereas PRKN, involved in removing dysfunctional mitochondria, was downregulated. Importantly, the transcriptome dynamics of the current study mirrored in-vivo human studies of acute CS exposure, chronic smokers, and inversely mirrored smoking cessation. Conclusion: These findings show that early after CS exposure xenobiotic metabolism and pro-inflammatory pathways were activated, followed by activation of the ferroptosis-related cell death pathway. Moreover, significant overlap between these transcriptomic responses in the in-vitro model and human in-vivo studies was found, with an early response of ciliated cells. These results provide validation for the use of ALI-PBEC cultures to study the human lung epithelial response to inhaled toxicants.

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How to cite

APA:

Van Der Does, A.M., Mahbub, R.M., Ninaber, D.K., Rathnayake, S.N.H., Timens, W., Van Den Berge, M.,... Faiz, A. (2022). Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa. Respiratory Research, 23(1). https://doi.org/10.1186/s12931-022-02150-2

MLA:

Van Der Does, Anne M., et al. "Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa." Respiratory Research 23.1 (2022).

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