tetano
Editor, Senior Moderator
Mol Neurobiol
. 2021 Oct 28.
doi: 10.1007/s12035-021-02593-6. Online ahead of print.
SARS-CoV-2 Spike Glycoprotein S1 Induces Neuroinflammation in BV-2 Microglia
Olumayokun A Olajide[SUP] 1 [/SUP], Victoria U Iwuanyanwu[SUP] 2 [/SUP], Oyinkansola D Adegbola[SUP] 2 [/SUP], Alaa A Al-Hindawi[SUP] 2 [/SUP]
Affiliations
Abstract
In addition to respiratory complications produced by SARS-CoV-2, accumulating evidence suggests that some neurological symptoms are associated with the disease caused by this coronavirus. In this study, we investigated the effects of the SARS-CoV-2 spike protein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF-α, IL-6, IL-1β and iNOS/NO. S1 also increased protein levels of phospho-p65 and phospho-IκBα, as well as enhanced DNA binding and transcriptional activity of NF-κB. These effects of the protein were blocked in the presence of BAY11-7082 (1 µM). Exposure of S1 to BV-2 microglia also increased the protein levels of NLRP3 inflammasome and enhanced caspase-1 activity. Increased protein levels of p38 MAPK was observed in BV-2 microglia stimulated with the spike protein S1 (100 ng/ml), an action that was reduced in the presence of SKF 86,002 (1 µM). Results of immunofluorescence microscopy showed an increase in TLR4 protein expression in S1-stimulated BV-2 microglia. Furthermore, pharmacological inhibition with TAK 242 (1 µM) and transfection with TLR4 small interfering RNA resulted in significant reduction in TNF-α and IL-6 production in S1-stimulated BV-2 microglia. These results have provided the first evidence demonstrating S1-induced neuroinflammation in BV-2 microglia. We propose that induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-κB and p38 MAPK, possibly as a result of TLR4 activation. These results contribute to our understanding of some of the mechanisms involved in CNS pathologies of SARS-CoV-2.
Keywords: Microglia; NF-κB; Neuroinflammation; SARS-CoV-2 spike protein S1; TLR4.
. 2021 Oct 28.
doi: 10.1007/s12035-021-02593-6. Online ahead of print.
SARS-CoV-2 Spike Glycoprotein S1 Induces Neuroinflammation in BV-2 Microglia
Olumayokun A Olajide[SUP] 1 [/SUP], Victoria U Iwuanyanwu[SUP] 2 [/SUP], Oyinkansola D Adegbola[SUP] 2 [/SUP], Alaa A Al-Hindawi[SUP] 2 [/SUP]
Affiliations
- PMID: 34709564
- DOI: 10.1007/s12035-021-02593-6
Abstract
In addition to respiratory complications produced by SARS-CoV-2, accumulating evidence suggests that some neurological symptoms are associated with the disease caused by this coronavirus. In this study, we investigated the effects of the SARS-CoV-2 spike protein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF-α, IL-6, IL-1β and iNOS/NO. S1 also increased protein levels of phospho-p65 and phospho-IκBα, as well as enhanced DNA binding and transcriptional activity of NF-κB. These effects of the protein were blocked in the presence of BAY11-7082 (1 µM). Exposure of S1 to BV-2 microglia also increased the protein levels of NLRP3 inflammasome and enhanced caspase-1 activity. Increased protein levels of p38 MAPK was observed in BV-2 microglia stimulated with the spike protein S1 (100 ng/ml), an action that was reduced in the presence of SKF 86,002 (1 µM). Results of immunofluorescence microscopy showed an increase in TLR4 protein expression in S1-stimulated BV-2 microglia. Furthermore, pharmacological inhibition with TAK 242 (1 µM) and transfection with TLR4 small interfering RNA resulted in significant reduction in TNF-α and IL-6 production in S1-stimulated BV-2 microglia. These results have provided the first evidence demonstrating S1-induced neuroinflammation in BV-2 microglia. We propose that induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-κB and p38 MAPK, possibly as a result of TLR4 activation. These results contribute to our understanding of some of the mechanisms involved in CNS pathologies of SARS-CoV-2.
Keywords: Microglia; NF-κB; Neuroinflammation; SARS-CoV-2 spike protein S1; TLR4.