Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice
| Autor: | Prabhleen Singh, Andrew Willeford, Mark Hepokoski, Joan Heller Brown, Laura E. Crotty Alexander, Jiang Tian, Zachary Yong, Ashley Du, John Shin, Christopher A. Drummond, A. Moshensky, Christian Javier, Denzil P. Mathew, Jasmine Lee, Kevin Vega, Ellen C. Breen, Soumita Das |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physiology Respiratory System Gene Expression Electronic Nicotine Delivery Systems Systemic inflammation Inbred C57BL Cardiovascular Medical and Health Sciences Mice Fibrosis Medicine 2.1 Biological and endogenous factors Nicotinic Agonists Barrier function systemic inflammation Mice Inbred ICR Blood-Air Barrier Inhalation Biological Sciences Inbred ICR Heart Disease Smoking and Health Respiratory Cytokines Female medicine.symptom Corrigendum Research Article medicine.medical_specialty Nicotine Primary Cell Culture Inflammation Respiratory Mucosa e-cigarette Proinflammatory cytokine 03 medical and health sciences cardiorenal dysfunction In vivo Physiology (medical) Internal medicine Tobacco Animals Humans business.industry fibrosis medicine.disease Mice Inbred C57BL electronic cigarette 030104 developmental biology Endocrinology Renal physiology business Digestive Diseases |
| Zdroj: | American journal of physiology. Regulatory, integrative and comparative physiology, vol 314, iss 6 Am J Physiol Regul Integr Comp Physiol Alexander, LEC; Drummond, CA; Hepokoski, M; Mathew, D; Moshensky, A; Willeford, A; et al.(2018). Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 314(6), R834-R847. doi: 10.1152/ajpregu.00270.2017. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/3cj3r0h3 |
| DOI: | 10.1152/ajpregu.00270.2017. |
| Popis: | Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction. C57BL/6 and CD-1 mice underwent nose only EV exposure daily for 3–6 mo, followed by cardiorenal physiological testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 min daily for 3–5 days before functional testing. Daily inhalation of EV increased circulating proinflammatory and profibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold) and EGF (25-fold). Proinflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs. 37 pg/ml, respectively; P < 0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% ( P = 0.017). Fibrosis, assessed by Masson’s trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; P < 0.05), heart (2.75-fold, C57BL/6 mice; P < 0.05), and liver (1.77-fold in CD-1; P < 0.0001). Gene expression changes demonstrated profibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate ( P < 0.01), and elevated blood pressure ( P = 0.016). These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease. |
| Databáze: | OpenAIRE |
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