Nicotine in Combination with SARS-CoV-2 Affects Cells Viability, Inflammatory Response and Ultrastructural Integrity.
Luigi SansoneAntonio de IureMario CristinaManuel BelliLaura VitielloFederica MarcolongoAlfredo RoselliniLisa MaceraPietro Giorgio SpeziaCarlo TominoStefano BonassiMatteo Antonio RussoFabrizio MaggiPatrizia RussoPublished in: International journal of molecular sciences (2022)
The aims of our study are to: (i) investigate the ability of nicotine to modulate the expression level of inflammatory cytokines in A549 cells infected with SARS-CoV-2; (ii) elucidate the ultrastructural features caused by the combination nicotine+SARS-CoV-2; and (iii) demonstrate the mechanism of action. In this study, A549 cells pretreated with nicotine were either exposed to LPS or poly(I:C), or infected with SARS-CoV-2. Treated and untreated cells were analyzed for cytokine production, cytotoxicity, and ultrastructural modifications. Vero E6 cells were used as a positive reference. Cells pretreated with nicotine showed a decrease of IL6 and TNFα in A549 cells induced by LPS or poly(I:C). In contrast, cells exposed to SARS-CoV-2 showed a high increase of IL6, IL8, IL10 and TNFα, high cytopathic effects that were dose- and time-dependent, and profound ultrastructural modifications. These modifications were characterized by membrane ruptures and fragmentation, the swelling of cytosol and mitochondria, the release of cytoplasmic content in extracellular spaces (including osmiophilic granules), the fragmentation of endoplasmic reticulum, and chromatin disorganization. Nicotine increased SARS-CoV-2 cytopathic effects, elevating the levels of inflammatory cytokines, and inducing severe cellular damage, with features resembling pyroptosis and necroptosis. The protective role of nicotine in COVID-19 is definitively ruled out.
Keyphrases
- sars cov
- induced apoptosis
- cell cycle arrest
- inflammatory response
- cell death
- respiratory syndrome coronavirus
- coronavirus disease
- endoplasmic reticulum stress
- oxidative stress
- magnetic resonance imaging
- computed tomography
- gene expression
- rheumatoid arthritis
- dna damage
- endoplasmic reticulum
- transcription factor
- early onset
- genome wide