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
© 2021. The Author(s)..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:44 |
|---|---|
| Enthalten in: |
Inflammation - 44(2021), 5 vom: 16. Okt., Seite 1865-1877 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Olajide, Olumayokun A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.10.2021 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s10753-021-01464-5 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM324156030 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM324156030 | ||
| 003 | DE-627 | ||
| 005 | 20231225185720.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s10753-021-01464-5 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1080.xml |
| 035 | |a (DE-627)NLM324156030 | ||
| 035 | |a (NLM)33860869 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Olajide, Olumayokun A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.10.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NF-KB | |
| 650 | 4 | |a PBMCs | |
| 650 | 4 | |a SARS-CoV-2 cytokine storm | |
| 650 | 4 | |a SARS-CoV-2 spike glycoprotein S1 | |
| 650 | 4 | |a inflammation | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 700 | 1 | |a Iwuanyanwu, Victoria U |e verfasserin |4 aut | |
| 700 | 1 | |a Lepiarz-Raba, Izabela |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Hindawi, Alaa A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Inflammation |d 1975 |g 44(2021), 5 vom: 16. Okt., Seite 1865-1877 |w (DE-627)NLM000293016 |x 1573-2576 |7 nnns |
| 773 | 1 | 8 | |g volume:44 |g year:2021 |g number:5 |g day:16 |g month:10 |g pages:1865-1877 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s10753-021-01464-5 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 44 |j 2021 |e 5 |b 16 |c 10 |h 1865-1877 | ||