The S1 subunits of SARS-CoV-2 variants differentially trigger the IL-6 signaling pathway in human brain endothelial cells and downstream impact on microglia activation.
Michael StangisDaniel AdesseBhavya SharmaEduardo CastroKush KumarNeil KumarMasha MinevichMichal ToborekPublished in: NeuroImmune pharmacology and therapeutics (2024)
Treatment with S1 derived from the D614 variant and from the Delta variant resulted in differential alterations of the IL-6 signaling pathway. Moreover, the HBMEC secretome obtained after exposure to the S1 subunit of the D614 variant activated STAT3 in microglial cells, indicating that proinflammatory signals from endothelial cells can propagate to other cells of the neurovascular unit. Overall, these results indicate the potential for different SARS-CoV-2 variants to induce unique cellular signatures and warrant individualized treatment strategies. The findings from this study also bring further awareness to proinflammatory responses involving brain microvasculature in COVID-19 and demonstrate how the surrounding microglia react to each unique variant derived response.
Keyphrases
- sars cov
- induced apoptosis
- signaling pathway
- endothelial cells
- cell cycle arrest
- pi k akt
- inflammatory response
- respiratory syndrome coronavirus
- endoplasmic reticulum stress
- neuropathic pain
- coronavirus disease
- epithelial mesenchymal transition
- copy number
- cell proliferation
- cell death
- spinal cord injury
- lipopolysaccharide induced
- dna methylation
- gene expression
- high glucose
- white matter
- resting state
- blood brain barrier
- brain injury
- vascular endothelial growth factor
- risk assessment
- cerebral ischemia
- functional connectivity
- human health
- replacement therapy