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Relative to traditional cigarettes, E-cigarette use is increasing due to the widespread perception of e-cigarettes being a healthier alternative. More recently, concern about e-cigarette use is rising after reports of dangerous health effects particularly in young users. This is kicking off a large number of studies which are investigating e-cigarettes and how components found in e-liquid such as nicotine, vitamin-E-acetate and propylene glycol (PG), are affecting pulmonary tissue health. Dr. Wang at the University of Rochester Medical Center is looking to address these questions in a recently published article1.

E-CIGARETTE-INDUCED PULMONARY INFLAMMATION

In their previous work, the expression of inflammatory hallmarks such as T cells and cytokines is put under investigation, showing dysregulated repair and inflammatory responses occur in a sex dependant manner following e-cigarette exposure2. E-cigarette aerosols containing nicotine appear to cause altered protein expression and lung airway remodelling. An increase in both nAChRα3 and nAChRα7 expression is a particularly strong trend in females after PG exposure.

They are continuing their efforts with by exposing subjects to propylene-glycol (PG), either with or without nicotine, in both male and female mice cohorts. Based upon the intriguing nAChR expression changes previously noted, these subject groups are additionally joined by a nAChRα7 KO mouse strain. Nicotinic acetylcholine receptors (nACHRs) are involved in the ACh signalling cascade in the central nervous system, and these receptors are also expressed within lung tissues3,4. nAChRα7 in particular is essential for Cholinergic Anti-Inflammatory Pathway (CAP) mediated inflammatory response pathway activation; a vital pathway connecting nervous and immune system responses5.

Dr. Wang found that the e-liquid carrier PG causes inflammatory influx into the lungs when delivered at sub-chronic levels and that removal of nAChRα7 activity was protective against this macrophage activation. The activation of both Cda4+ and CD8a+ T-lymphocyte types and various cytokines appear to be ameliorated in the KO group (Figure 1).  They demonstrate that e-cigarette aerosol exposure results in a dysregulated repair process, with changes in the expression of Matric metalloproteinases (MMPs), Extracellular Matrix (ECM) proteins and p50/p1015, components of widespread regulatory complex Nuclear Factor Kappa light-chain-enhancer (NF-kB). These changes are most evident when the e-liquid contains nicotine and seems to require nAChRα7, as the response profile is dramatically changed where this receptor is absent.

If you are interested in more details about e-cigarette or ENDS exposure studies, please visit the Application and inExpose information pages or reach out to discuss your studies directly with one of our Application Specialists.The results of this publication suggest a sex-specific, key mediatory role of nAchRα7 in the inflammatory response that is triggered by e-liquid exposure. This result is robust both without (PG only) or e-liquid containing nicotine (PG+ nicotine) however the response characteristics differ in each sex. Further studies to examine epithelial vs fibroblast lung cell differences after e-cigarette exposure and including subject groups with altered nAChRα7 expression are called for by the authors. It is hoped that future findings will provide greater insight into clinical effects seen in e-cigarette users.

Read more about ENDS exposure solutions and the development of translatable models here.

References

1Wang et al. Pre-print 2020. E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChRα7 Receptor: Role of nAChRα7 in ACE2 Covid-19 receptor regulation. DOI:10.21203/rs.2.23829/v2

2Wang et al. 2019. Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung. FASEB BioAdvances; 1:609–623. DOI:10.1096/fba.2019-00048

3Minna, JD. Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer. The Journal of clinical investigation ;111:31‐33

4Zia et al. 1997. Nicotine enhances expression of the alpha 3, alpha 4, alpha 5, and alpha 7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells. Research communications in molecular pathology and pharmacology; 97:243‐262.

5 Baez-Pagan et al. 2015. Activation of the Macrophage α7 Nicotinic Acetylcholine Receptor and Control of Inflammation. Journal of Neuroimmune Pharmolocogy; 10(3): 468–476. DOI:10.1007/s11481

 

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