E-cigarette flavored pods induce inflammation, epithelial barrier dysfunction, and DNA damage in lung epithelial cells and monocytes

Scientific Reports

Volumn 9, Issue 1, 2019, Pages

  Muthumalage, Thivanka ^a   Lamb, Thomas ^a   Friedman, Michelle R ^b   Rahman, Irfan ^a  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b STATE UNIVERSITY OF NEW YORK   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLAVORING AGENT; INTERLEUKIN 8; PROSTAGLANDIN E2; SUPEROXIDE;

CELL LINE; DNA DAMAGE; DRUG EFFECT; ELECTRONIC CIGARETTE; EPITHELIUM; EPITHELIUM CELL; HUMAN; INFLAMMATION; LUNG; METABOLISM; MITOCHONDRION; MONOCYTE; PATHOLOGY; PATHOPHYSIOLOGY;

CELL LINE; DINOPROSTONE; DNA DAMAGE; ELECTRONIC NICOTINE DELIVERY SYSTEMS; EPITHELIAL CELLS; EPITHELIUM; FLAVORING AGENTS; HUMANS; INFLAMMATION; INTERLEUKIN-8; LUNG; MITOCHONDRIA; MONOCYTES; SUPEROXIDES;

EID: 85076473985     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-019-51643-6     Document Type: Article

References (40)

1. Bals, R. et al. Electronic cigarettes: a task force report from the European Respiratory Society. Eur Respir J 53, 10.1183/13993003.01151-2018 (2019).
2. Kaur, G., Muthumalage, T. & Rahman, I. Mechanisms of toxicity and biomarkers of flavoring and flavor enhancing chemicals in emerging tobacco and non-tobacco products. Toxicol Lett 288, 143–155, 10.1016/j.toxlet.2018.02.025 (2018).
3. Muthumalage, T. et al. Inflammatory and Oxidative Responses Induced by Exposure to Commonly Used e-Cigarette Flavoring Chemicals and Flavored e-Liquids without Nicotine. Front Physiol 8, 1130, 10.3389/fphys.2017.01130 (2017).
4. Waris, G. & Ahsan, H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 5, 14, 10.1186/1477-3163-5-14 (2006).
5. Cullen, K. A. et al. Notes from the Field: Use of Electronic Cigarettes and Any Tobacco Product Among Middle and High School Students - United States, 2011-2018. MMWR Morb Mortal Wkly Rep 67, 1276–1277, 10.15585/mmwr.mm6745a5 (2018).
6. Ramamurthi, D., Chau, C. & Jackler, R. K. JUUL and other stealth vaporisers: hiding the habit from parents and teachers. Tob Control, 10.1136/tobaccocontrol-2018-054455 (2018).
7. Nardone, N., Helen, G. S., Addo, N., Meighan, S. & Benowitz, N. L. JUUL electronic cigarettes: Nicotine exposure and the user experience. Drug Alcohol Depend 203, 83–87, 10.1016/j.drugalcdep.2019.05.019 (2019).
8. Landry, R. L. et al. The role of flavors in vaping initiation and satisfaction among U.S. adults. Addict Behav 99, 106077, 10.1016/j.addbeh.2019.106077 (2019).
9. Leavens, E. L. S., Stevens, E. M., Brett, E. I., Leffingwell, T. R. & Wagener, T. L. JUUL in school: JUUL electronic cigarette use patterns, reasons for use, and social normative perceptions among college student ever users. Addict Behav 99, 106047, 10.1016/j.addbeh.2019.106047 (2019).
10. Duell, A. K., Pankow, J. F. & Peyton, D. H. Free-Base Nicotine Determination in Electronic Cigarette Liquids by (1)H NMR Spectroscopy. Chem Res Toxicol 31, 431–434, 10.1021/acs.chemrestox.8b00097 (2018).
11. Omaiye, E. E., McWhirter, K. J., Luo, W., Pankow, J. F. & Talbot, P. High-Nicotine Electronic Cigarette Products: Toxicity of JUUL Fluids and Aerosols Correlates Strongly with Nicotine and Some Flavor Chemical Concentrations. Chem Res Toxicol, 10.1021/acs.chemrestox.8b00381 (2019).
12. McKeganey, N. & Russell, C. Prevalence of Awareness and Use of JUUL E-cigarettes in a National Probability Sample of Adolescents in the United States. Am J Health Behav 43, 591–605, 10.5993/AJHB.43.3.13 (2019).
13. Jackler, R. K. & Ramamurthi, D. Nicotine arms race: JUUL and the high-nicotine product market. Tob Control, 10.1136/tobaccocontrol-2018-054796 (2019).
14. Erythropel, H. C. et al. Flavorant-Solvent Reaction Products and Menthol in JUUL E-Cigarettes and Aerosol. Am J Prev Med 57, 425–427, 10.1016/j.amepre.2019.04.004 (2019).
15. Gerloff, J. et al. Inflammatory Response and Barrier Dysfunction by Different e-Cigarette Flavoring Chemicals Identified by Gas Chromatography-Mass Spectrometry in e-Liquids and e-Vapors on Human Lung Epithelial Cells and Fibroblasts. Appl In Vitro Toxicol 3, 28–40, 10.1089/aivt.2016.0030 (2017).
16. Reilly, S. M., Bitzer, Z. T., Goel, R., Trushin, N. & Richie, J. P., Jr. Free Radical, Carbonyl, and Nicotine Levels Produced by Juul Electronic Cigarettes. Nicotine Tob Res, 10.1093/ntr/nty221 (2018).
17. Son, Y. et al. Hydroxyl Radicals in E-Cigarette Vapor and E-Vapor Oxidative Potentials under Different Vaping Patterns. Chem Res Toxicol. 10.1021/acs.chemrestox.8b00400 (2019).
18. Haddad, C. et al. Reactive Oxygen Species Emissions from Supra- and Sub-Ohm Electronic Cigarettes. J Anal Toxicol 43, 45–50, 10.1093/jat/bky065 (2019).
19. Naik, E. & Dixit, V. M. Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J Exp Med 208, 417–420, 10.1084/jem.20110367 (2011).
20. Aravamudan, B. et al. Cigarette smoke-induced mitochondrial fragmentation and dysfunction in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 306, L840–854, 10.1152/ajplung.00155.2013 (2014).
21. Chen, L. et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9, 7204–7218, 10.18632/oncotarget.23208 (2018).
22. Mukaida, N. Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol 284, L566–577, 10.1152/ajplung.00233.2002 (2003).
23. Viswam, D., Trotter, S., Burge, P. S. & Walters, G. I. Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes. BMJ Case Rep 2018, 10.1136/bcr-2018-224350 (2018).
24. Bozyk, P. D. & Moore, B. B. Prostaglandin E2 and the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol 45, 445–452, 10.1165/rcmb.2011-0025RT (2011).
25. Lappalainen, U., Whitsett, J. A., Wert, S. E., Tichelaar, J. W. & Bry, K. Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am J Respir Cell Mol Biol 32, 311–318, 10.1165/rcmb.2004-0309OC (2005).
26. Ma, B. et al. Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema. J Clin Invest 115, 3460–3472, 10.1172/JCI24858 (2005).
27. Moore, B. B. et al. GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism. J Immunol 165, 4032–4039, 10.4049/jimmunol.165.7.4032 (2000).
28. Munakata, S. et al. Oxidative stress responses in human bronchial epithelial cells exposed to cigarette smoke and vapor from tobacco- and nicotine-containing products. Regul Toxicol Pharmacol 99, 122–128, 10.1016/j.yrtph.2018.09.009 (2018).
29. Tsantikos, E. et al. Granulocyte-CSF links destructive inflammation and comorbidities in obstructive lung disease. J Clin Invest 128, 2406–2418, 10.1172/JCI98224 (2018).
30. Wahl, S. M., Wong, H. & McCartney-Francis, N. Role of growth factors in inflammation and repair. J Cell Biochem 40, 193–199, 10.1002/jcb.240400208 (1989).
31. Brock, C. S. & Lee, S. M. Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer. Eur Respir J 19, 557–570, 10.1183/09031936.02.00293002 (2002).
32. Crotty Alexander, L. E. et al. Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice. Am J Physiol Regul Integr Comp Physiol 314, R834–R847, 10.1152/ajpregu.00270.2017 (2018).
33. Muro, S. et al. Expression of IL-15 in inflammatory pulmonary diseases. J Allergy Clin Immunol 108, 970–975, 10.1067/mai.2001.119556 (2001).
34. Ge, N. et al. Synthesis and secretion of interleukin-15 by freshly isolated human bronchial epithelial cells. Int Arch Allergy Immunol 135, 235–242, 10.1159/000081309 (2004).
35. Nishida, K. et al. Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension. Am J Physiol Lung Cell Mol Physiol 313, L581–L591, 10.1152/ajplung.00074.2017 (2017).
36. Aghapour, M., Raee, P., Moghaddam, S. J., Hiemstra, P. S. & Heijink, I. H. Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease: Role of Cigarette Smoke Exposure. Am J Respir Cell Mol Biol 58, 157–169, 10.1165/rcmb.2017-0200TR (2018).
37. Lin, V. Y. et al. Vaporized E-Cigarette Liquids Induce Ion Transport Dysfunction in Airway Epithelia. Am J Respir Cell Mol Biol 61, 162–173, 10.1165/rcmb.2017-0432OC (2019).
38. Lee, H. W. et al. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc Natl Acad Sci USA 115, E1560–E1569, 10.1073/pnas.1718185115 (2018).
39. Canistro, D. et al. E-cigarettes induce toxicological effects that can raise the cancer risk. Sci Rep 7, 2028, 10.1038/s41598-017-02317-8 (2017).
40. Benowitz, N. L. & Fraiman, J. B. Cardiovascular effects of electronic cigarettes. Nat Rev Cardiol 14, 447–456, 10.1038/nrcardio.2017.36 (2017).