Transcriptomic Analysis of Tobacco-flavored E-cigarette and Menthol-flavored E-cigarette Exposure in the Human Middle Ear

Overview

Journal Sci Rep

Specialty Science

Date 2020 Nov 28

PMID 33247188

Citations 3

Authors

Jae-Jun Song

Yoon Young Go

Jong Kyou Lee

Bum Sang Lee

Su-Kyoung Park

Harry Jung

Jun Ho Lee

Jiwon Chang

Affiliations

Soon will be listed here.

Abstract

Electronic cigarettes (e-cigarettes) are the most widely used electronic nicotine delivery systems and are designed to imitate smoking and aid in smoking cessation. Although the number of e-cigarette users is increasing rapidly, especially among young adults and adolescents, the potential health impacts and biologic effects of e-cigarettes still need to be elucidated. Our previous study demonstrated the cytotoxic effects of electronic liquids (e-liquids) in a human middle ear epithelial cell (HMEEC-1) line, which were affected by the manufacturer and flavoring agents regardless of the presence of nicotine. In this study, we aimed to evaluate the gene expression profile and identify potential molecular modulator genes and pathways in HMEEC-1 exposed to two different e-liquids (tobacco- and menthol-flavored). HMEEC-1 was exposed to e-liquids, and RNA sequencing, functional analysis, and pathway analysis were conducted to identify the resultant transcriptomic changes. A total of 843 genes were differentially expressed following exposure to the tobacco-flavored e-liquid, among which 262 genes were upregulated and 581 were downregulated. Upon exposure to the menthol-flavored e-liquid, a total of 589 genes were differentially expressed, among which 228 genes were upregulated and 361 were downregulated. Among the signaling pathways associated with the differentially expressed genes mediated by tobacco-flavored e-liquid exposure, several key molecular genes were identified, including IL6 (interleukin 6), PTGS2 (prostaglandin-endoperoxide synthase 2), CXCL8 (C-X-C motif chemokine ligand 8), JUN (Jun proto-oncogene), FOS (Fos proto-oncogene), and TP53 (tumor protein 53). Under menthol-flavored e-liquid treatment, MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), MYC (MYC proto-oncogene, bHLH transcription factor), HMOX1 (heme oxygenase 1), NOS3 (nitric oxide synthase 3), and CAV1 (caveolin 1) were predicted as key genes. In addition, we identified related cellular processes, including inflammatory responses, oxidative stress and carcinogenesis, under exposure to tobacco- and menthol-flavored e-liquids. We identified differentially expressed genes and related cellular processes and gene signaling pathways after e-cigarette exposure in human middle ear cells. These findings may provide useful evidence for understanding the effect of e-cigarette exposure.

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References

Sherwood C, Boitano S . Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine. Respir Res. 2016; 17(1):57. PMC: 4869201. DOI: 10.1186/s12931-016-0369-9. View

Bahl V, Lin S, Xu N, Davis B, Wang Y, Talbot P . Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Reprod Toxicol. 2012; 34(4):529-37. DOI: 10.1016/j.reprotox.2012.08.001. View

Tierney P, Karpinski C, Brown J, Luo W, Pankow J . Flavour chemicals in electronic cigarette fluids. Tob Control. 2015; 25(e1):e10-5. PMC: 4853541. DOI: 10.1136/tobaccocontrol-2014-052175. View

Zanetti F, Titz B, Sewer A, Lo Sasso G, Scotti E, Schlage W . Comparative systems toxicology analysis of cigarette smoke and aerosol from a candidate modified risk tobacco product in organotypic human gingival epithelial cultures: A 3-day repeated exposure study. Food Chem Toxicol. 2016; 101:15-35. DOI: 10.1016/j.fct.2016.12.027. View

Jiang H, Lei R, Ding S, Zhu S . Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads. BMC Bioinformatics. 2014; 15:182. PMC: 4074385. DOI: 10.1186/1471-2105-15-182. View

Alzahrani T, Pena I, Temesgen N, Glantz S . Association Between Electronic Cigarette Use and Myocardial Infarction. Am J Prev Med. 2018; 55(4):455-461. PMC: 6208321. DOI: 10.1016/j.amepre.2018.05.004. View

Kleinschmidt E, Schlaepfer D . Focal adhesion kinase signaling in unexpected places. Curr Opin Cell Biol. 2017; 45:24-30. PMC: 5482783. DOI: 10.1016/j.ceb.2017.01.003. View

Szostak J, Boue S, Talikka M, Guedj E, Martin F, Phillips B . Aerosol from Tobacco Heating System 2.2 has reduced impact on mouse heart gene expression compared with cigarette smoke. Food Chem Toxicol. 2017; 101:157-167. DOI: 10.1016/j.fct.2017.01.013. View

Cao D, Aldy K, Hsu S, McGetrick M, Verbeck G, De Silva I . Review of Health Consequences of Electronic Cigarettes and the Outbreak of Electronic Cigarette, or Vaping, Product Use-Associated Lung Injury. J Med Toxicol. 2020; 16(3):295-310. PMC: 7320089. DOI: 10.1007/s13181-020-00772-w. View

10.

McConnell R, Barrington-Trimis J, Wang K, Urman R, Hong H, Unger J . Electronic Cigarette Use and Respiratory Symptoms in Adolescents. Am J Respir Crit Care Med. 2016; 195(8):1043-1049. PMC: 5422647. DOI: 10.1164/rccm.201604-0804OC. View

11.

Lerner C, Sundar I, Yao H, Gerloff J, Ossip D, McIntosh S . Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung. PLoS One. 2015; 10(2):e0116732. PMC: 4319729. DOI: 10.1371/journal.pone.0116732. View

12.

Thorne D, Larard S, Baxter A, Meredith C, Gaa M . The comparative in vitro assessment of e-cigarette and cigarette smoke aerosols using the γH2AX assay and applied dose measurements. Toxicol Lett. 2016; 265:170-178. DOI: 10.1016/j.toxlet.2016.12.006. View

13.

Brown C, Cheng J . Electronic cigarettes: product characterisation and design considerations. Tob Control. 2014; 23 Suppl 2:ii4-10. PMC: 3995271. DOI: 10.1136/tobaccocontrol-2013-051476. View

14.

Lechasseur A, Jubinville E, Routhier J, Berube J, Hamel-Auger M, Talbot M . Exposure to electronic cigarette vapors affects pulmonary and systemic expression of circadian molecular clock genes. Physiol Rep. 2017; 5(19). PMC: 5641932. DOI: 10.14814/phy2.13440. View

15.

Cheng T . Chemical evaluation of electronic cigarettes. Tob Control. 2014; 23 Suppl 2:ii11-7. PMC: 3995255. DOI: 10.1136/tobaccocontrol-2013-051482. View

16.

Chun Y, Moon S, Lee H, Webster P, Brackmann D, Rhim J . Immortalization of normal adult human middle ear epithelial cells using a retrovirus containing the E6/E7 genes of human papillomavirus type 16. Ann Otol Rhinol Laryngol. 2002; 111(6):507-17. DOI: 10.1177/000348940211100606. View

17.

Varlet V, Farsalinos K, Augsburger M, Thomas A, Etter J . Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health. 2015; 12(5):4796-815. PMC: 4454939. DOI: 10.3390/ijerph120504796. View

18.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

19.

Glantz S . The Evidence of Electronic Cigarette Risks Is Catching Up With Public Perception. JAMA Netw Open. 2019; 2(3):e191032. DOI: 10.1001/jamanetworkopen.2019.1032. View

20.

Li G, Saad S, Oliver B, Chen H . Heat or Burn? Impacts of Intrauterine Tobacco Smoke and E-Cigarette Vapor Exposure on the Offspring's Health Outcome. Toxics. 2018; 6(3). PMC: 6160993. DOI: 10.3390/toxics6030043. View