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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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Primary bronchial epithelial cells (PBEC) were differentiated at the air\u2013liquid interface (ALI) and exposed to whole CS. Bulk RNA-sequencing was performed at 1\u00a0h, 4\u00a0h, and 24\u00a0h hereafter, followed by differential gene expression analysis. Results were additionally compared to data retrieved from human CS studies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>ALI-PBEC gene expression in response to CS was most significantly changed at 4\u00a0h after exposure. Early transcriptomic changes (1\u00a0h, 4\u00a0h 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\u00a0h, ferroptosis-associated genes were significantly increased, whereas <jats:italic>PRKN<\/jats:italic>, involved in removing dysfunctional mitochondria, was downregulated. Importantly, the transcriptome dynamics of the current study mirrored <jats:italic>in-vivo<\/jats:italic> human studies of acute CS exposure, chronic smokers, and inversely mirrored smoking cessation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>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 <jats:italic>in-vitro<\/jats:italic> model and human <jats:italic>in-vivo<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-022-02150-2","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T12:04:08Z","timestamp":1662120248000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa"],"prefix":"10.1186","volume":"23","author":[{"given":"Anne M.","family":"van der Does","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashad M.","family":"Mahbub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis K.","family":"Ninaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senani N. 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Patients from which this lung tissue was derived were enrolled in the biobank via a no-objection system for coded anonymous further use of such tissue (www.federa.org). However, since 29-11-2020, patients are enrolled in the biobank using active informed consent in accordance with local regulations from the LUMC biobank with approval by the institutional medical ethical committee (B20.042\/Ab\/ab and B20.042\/Kb\/kb).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"227"}}