ArticleFrontiers in immunology2022
SARS-CoV-2 modulates inflammatory responses of alveolar epithelial type II cells
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The Vitamin D Serum Levels in Pregnant Women Affected by COVID-19: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- Host metabolic responses to SARS-CoV-2 and influenza viruses: parallels and contrasts.Metabolomics : Official journal of the Metabolomic Society · 2026Review
- Leveraging ADMET Profiling, Network Pharmacology, and Molecular Docking to Evaluate the Repurposing of Product Nkabinde for COVID-19 Treatment.Biomedicines · 2026Article
- Viral Pathogens and Pulmonary Fibrosis: EMT-Driven Mechanisms and Insights From Traditional Chinese Medicine.Reviews in medical virology · 2026Review
- Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.Children (Basel, Switzerland) · 2025Review
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- Luteolin-Rich Extract fromLife (Basel, Switzerland) · 2025Article
- Inhibition of LPS-induced inflammation and signaling pathways in fallopian tube epithelial cells by estrogen and progesterone.BMC veterinary research · 2025Article
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- TLR2 Activation as a Marker of Severe COVID-19 and a Potential Therapeutic Target.Current medicinal chemistry · 2025Review
- High-altitude immune remodeling in children withFrontiers in immunology · 2025Article
- Autophagy-enhancing strategies to promote intestinal viral resistance and mucosal barrier function in SARS-CoV-2 infection.Autophagy reports · 2025Article
- The Role of Inflammation in the Pathogenesis of Viral Respiratory Infections.Microorganisms · 2024Review
- In Silico Exploration of CD200 as a Therapeutic Target for COVID-19.Microorganisms · 2024Article
- The Medicinal Species of the Lycium Genus (Goji Berries) in East Asia: A Review of Its Effect on Cell Signal Transduction Pathways.Plants (Basel, Switzerland) · 2024Review
- Review
- Ginseng and ginsenosides on cardiovascular and pulmonary diseases; Pharmacological potentials for the coronavirus (COVID-19).Journal of ginseng research · 2024Review
- Analysis of transcriptomics data from COVID-19 patients: a pilot research.Folia microbiologica · 2024Article
- Nintedanib Mitigates Radiation-Induced Pulmonary Fibrosis by Suppressing Epithelial Cell Inflammatory Response and Inhibiting Fibroblast-to-Myofibroblast Transition.International journal of biological sciences · 2024Article
- Cognitive Impairment in Multiple Sclerosis.Bioengineering (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: SARS-CoV-2 infects through the respiratory route and triggers inflammatory response by affecting multiple cell types including type II alveolar epithelial cells. SARS-CoV-2 triggers signals Aim: Aim of the present study was to investigate the effect of SARS-CoV2 on type II alveolar epithelial cells, focusing on signals initiated by its S protein and their impact on the expression of inflammatory mediators. Results: For this purpose A549 alveolar type II epithelial cells were exposed to SARS CoV2 S recombinant protein and the expression of inflammatory mediators was measured. The results showed that SARS-CoV-2 S protein decreased the expression and secretion of IL8, IL6 and TNFα, 6 hours following stimulation, while it had no effect on IFNα, CXCL5 and PAI-1 expression. We further examined whether SARS-CoV-2 S protein, when combined with TLR2 signals, which are also triggered by SARS-CoV2 and its envelope protein, exerts a different effect in type II alveolar epithelial cells. Simultaneous treatment of A549 cells with SARS-CoV-2 S protein and the TLR2 ligand PAM3csk4 decreased secretion of IL8, IL6 and TNFα, while it significantly increased IFNα, CXCL5 and PAI-1 mRNA expression. To investigate the molecular pathway through which SARS-CoV-2 S protein exerted this immunomodulatory action in alveolar epithelial cells, we measured the induction of MAPK/ERK and PI3K/AKT pathways and found that SARS-CoV-2 S protein induced the activation of the serine threonine kinase AKT. Treatment with the Akt inhibitor MK-2206, abolished the inhibitory effect of SARS-CoV-2 S protein on IL8, IL6 and TNFα expression, suggesting that SARS-CoV-2 S protein mediated its action Conclusion: The findings of our study, showed that SARS-CoV-2 S protein suppressed inflammatory responses in alveolar epithelial type II cells at early stages of infection through activation of the PI3K/AKT pathway. Thus, our results suggest that at early stages SARS-CoV-2 S protein signals inhibit immune responses to the virus allowing it to propagate the infection while in combination with TLR2 signals enhances PAI-1 expression, potentially affecting the local coagulation cascade.
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