Frontiers in Immunology (Dec 2021)

IL1β Promotes TMPRSS2 Expression and SARS-CoV-2 Cell Entry Through the p38 MAPK-GATA2 Axis

  • Chiara Cioccarelli,
  • Chiara Cioccarelli,
  • Ricardo Sánchez-Rodríguez,
  • Ricardo Sánchez-Rodríguez,
  • Roberta Angioni,
  • Roberta Angioni,
  • Francisca C. Venegas,
  • Francisca C. Venegas,
  • Nicole Bertoldi,
  • Nicole Bertoldi,
  • Fabio Munari,
  • Fabio Munari,
  • Annamaria Cattelan,
  • Barbara Molon,
  • Barbara Molon,
  • Antonella Viola,
  • Antonella Viola

DOI
https://doi.org/10.3389/fimmu.2021.781352
Journal volume & issue
Vol. 12

Abstract

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After the outburst of the SARS-CoV-2 pandemic, a worldwide research effort has led to the uncovering of many aspects of the COVID-19, among which we can count the outstanding role played by inflammatory cytokine milieu in the disease progression. Despite that, molecular mechanisms that regulate SARS-CoV-2 pathogenesis are still almost unidentified. In this study, we investigated whether the pro-inflammatory milieu of the host affects the susceptibility of SARS-CoV-2 infection by modulating ACE2 and TMPRSS2 expression. Our results indicated that the host inflammatory milieu favors SARS-CoV-2 infection by directly increasing TMPRSS2 expression. We unveiled the molecular mechanism that regulates this process and that can be therapeutically advantageously targeted.

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