ArticleInflammation2021
Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone.
Article in Inflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 66 citations in OpenAlex.
- Involvement of NLRP3 Inflammasome in Methamphetamine Augmentation of SARS-CoV-2 N-Protein-Induced Neuroinflammation in Rat Microglial Cells.International journal of molecular sciences · 2026Article
- FNDC4 and FNDC5 Attenuate SARS-CoV-2 S1-Induced Inflammatory Responses in Human Adipose Tissue.European journal of clinical investigation · 2026Article
- Recombinant SARS-Cov-2 spike protein S1 subunit upregulates P2 × 7-NLRP3 leading to macrophage pyroptosis promoting acute lung injury.Respiratory research · 2026Article
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- COVID-19 Induces Greater NLRP3 Inflammasome Activation in Obese Patients than Other Chronic Illnesses: A Case-Control Study.International journal of molecular sciences · 2025Article
- The recombinant spike S1 protein induces injury and inflammation in co-cultures of human alveolar epithelial cells and macrophages.PloS one · 2025Article
- The selective ERβ agonist AC 186 reduces polyinosinic:polycytidylic acid (poly I:C)-induced inflammatory responses in BEAS-2B lung epithelial cells.Frontiers in pharmacology · 2025Article
- Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies.Viruses · 2024Review
- Inhibitory Effect of Luteolin on Spike S1 Glycoprotein-Induced Inflammation in THP-1 Cells via the ER Stress-Inducing Calcium/CHOP/MAPK Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Inhibition of SARS-CoV-2-Induced NLRP3 Inflammasome-Mediated Lung Cell Inflammation by Triphala-Loaded Nanoparticle Targeting Spike Glycoprotein S1.Pharmaceutics · 2024Article
- Pulmonary inflammation and viral replication define distinct clinical outcomes in fatal cases of COVID-19.PLoS pathogens · 2024Article
- Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19.Inflammopharmacology · 2024Review
- Review
- Multifaceted role of SARS-CoV-2 structural proteins in lung injury.Frontiers in immunology · 2024Review
- Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients.Frontiers in immunology · 2024Article
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
- Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.Clinical and experimental medicine · 2023Review
- NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis.Cardiovascular research · 2023Article
- Cytokine Response Following SARS-CoV-2 Antigen Stimulation in Patients with Predominantly Antibody Deficiencies.Viruses · 2023Article
- The Impact of COVID-19 on People Living with HIV-1 and HIV-1-Associated Neurological Complications.Viruses · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An understanding of the pathological inflammatory mechanisms involved in SARS-CoV-2 virus infection is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 cytokine storm. In this study, the effects of a recombinant SARS-CoV-2 spike glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation of PBMCs with spike glycoprotein S1 (100 ng/mL) resulted in significant elevation in the production of TNFα, IL-6, IL-1β and IL-8. However, pre-treatment with dexamethasone (100 nM) caused significant reduction in the release of these cytokines. Further experiments revealed that S1 stimulation of PBMCs increased phosphorylation of NF-κB p65 and IκBα, and IκBα degradation. DNA binding of NF-κB p65 was also significantly increased following stimulation with spike glycoprotein S1. Treatment of PBMCs with dexamethasone (100 nM) or BAY11-7082 (1 μM) resulted in inhibition of spike glycoprotein S1-induced NF-κB activation. Activation of p38 MAPK by S1 was blocked in the presence of dexamethasone and SKF 86002. CRID3, but not dexamethasone pre-treatment, produced significant inhibition of S1-induced activation of NLRP3/caspase-1. Further experiments revealed that S1-induced increase in the production of TNFα, IL-6, IL-1β and IL-8 was reduced in the presence of BAY11-7082 and SKF 86002, while CRID3 pre-treatment resulted in the reduction of IL-1β production. These results suggest that SARS-CoV-2 spike glycoprotein S1 stimulated PBMCs to release pro-inflammatory cytokines through mechanisms involving activation of NF-κB, p38 MAPK and NLRP3 inflammasome. It is proposed that the clinical benefits of dexamethasone in COVID-19 are possibly due to its anti-inflammatory activity in reducing SARS-CoV-2 cytokine storm.
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