The effects of E-cigarettes on pulmonary inflammation and inflammasome activation

Abstract

E-cigarettes vaporise a mixture of Propylene Glycol (PG) and Vegetable Glycerine (VG) with nicotine and flavourings as additional constituents. In vitro, flavoured and nicotine containing vapours induce significant cytotoxicity, promote inflammatory cytokine release and reactive oxygen species generation. Inflammatory complexes called the inflammasomes are known to initiate and potentiate inflammation and are classically activated by two signals, usually a PAMP (Pathogen Associated Molecular Pattern) and a DAMP (Danger Associated Molecular Pattern) which result in the processing of capsase-1, interleukins 1ȕ and 18, along with gasdermin D, leading to inflammatory cell death called pyroptosis. As E-vapour has been shown to have pro-inflammatory effects on pulmonary cells, it is possible that vapours or vapour components could lead to inflammasome activation.

The hypothesis of this thesis was that E-vapour induces inflammatory cytokine release and activates the inflammasomes. This was investigated by adding PG and VG, with and without nicotine, as liquids and vapours, to human macrophages and epithelial cells. A549 epithelial cells, THP-1 macrophages and primary macrophages isolated from smoking and non-smoking individuals were treated with E-liquid, E-vapours and inflammasome stimuli.

E -vapours and liquids were not cytotoxic to macrophages or epithelial cells. E-vapours also reduced IL-8 expression from resting epithelial cells and macrophages and from TNFĮ activated epithelial cells. In relation to inflammasome activation, E-vapours acted as a signal 2 DAMP in LPS primed macrophages but not in epithelial cells. Conversely, when macrophages were stimulated with classical inflammasome activators, LPS and Nigericin, the simultaneous addition of E-vapour with these signals reduced inflammasome activation. Analysis of BAL from E-cigarette users and smokers after LPS inhalation showed a similar inflammatory profile as measured by inflammatory cytokine and acute phase protein content. These data highlight that vaporisation of E-liquid produces vapours that are not benign to human cells and can cause inflammatory dysregulation.

Date of Award	Dec 2020
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Murali Shyamsundar (Supervisor), Cecilia O'Kane (Supervisor) & Yvonne Dombrowski (Supervisor)