Exaggerated cytokine production in human peripheral blood mononuclear cells by recombinant SARS-CoV-2 spike glycoprotein S1 and its inhibition by dexamethasone

作者: Olumayokun A Olajide , Izabela Lepiarz-Raba , Victoria U Iwuanyanwu , Alaa A Al-Hindawi

DOI: 10.1101/2021.02.03.429536

关键词:

摘要: An understanding of the pathological inflammatory mechanisms involved in SARS-CoV-2 virus infection is necessary order to discover new molecular pharmacological targets for spike glycoprotein. In this study, effects a recombinant glycoprotein S1 was investigated human peripheral blood mononuclear cells (PBMCs). Stimulation with (100 ng/mL) resulted significant elevation production TNF, IL-6, IL-1{beta} and IL-8. However, pre-treatment dexamethasone nM) caused reduction release these cytokines. Further experiments revealed that stimulation PBMCs increased phosphorylation NF-{kappa}B p65 I{kappa}B, while increasing I{kappa}B degradation. DNA binding also significantly following S1. Treatment or BAY11 -7082 (1 M) inhibition -induced activation. Activation p38 MAPK by blocked presence SKF 86002. CRID3, but not produced S1-induced activation NLRP3/caspase-1. increase IL-8 reduced BAY11-7082 86002, CRID3 production. These results suggest stimulate pro-inflammatory cytokines through involving NF-{kappa}B, NLRP3 inflammasome. It proposed clinical benefits COVID-19 possibly due its anti-inflammatory activity reducing cytokine storm.

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