SARS‑CoV‑2 spike protein‑induced host inflammatory response signature in human corneal epithelial cells

Mol Med Rep. 2021 Aug;24(2):584. doi: 10.3892/mmr.2021.12223. Epub 2021 Jun 16.

Abstract

Coronavirus disease 2019 (COVID‑19), caused by the severe acute respiratory syndrome coronavirus‑2 (SARS‑CoV‑2), led to an outbreak of viral pneumonia in December 2019. The present study aimed to investigate the host inflammatory response signature‑caused by SARS‑CoV‑2 in human corneal epithelial cells (HCECs). The expression level of angiotensin‑converting enzyme 2 (ACE2) in the human cornea was determined via immunofluorescence. In vitro experiments were performed in HCECs stimulated with the SARS‑CoV‑2 spike protein. Moreover, the expression levels of ACE2, IL‑8, TNF‑α, IL‑6, gasdermin D (GSDMD) and IL‑1β in HCECs were detected using reverse transcription‑quantitative PCR and/or western blotting. It was identified that ACE2 was expressed in normal human corneal epithelium and HCECs cultured in vitro. Furthermore, the expression levels of IL‑8, TNF‑α and IL‑6 in HCECs were decreased following SARS‑CoV‑2 spike protein stimulation, while the expression levels of GSDMD and IL‑1β were increased. In conclusion, the present results demonstrated that the SARS‑CoV‑2 spike protein suppressed the host inflammatory response and induced pyroptosis in HCECs. Therefore, blocking the ACE2 receptor in HCECs may reduce the infection rate of COVID‑19.

Keywords: ACE2; COVID‑19; GSDMD; SARS‑CoV‑2; cornea; human corneal epithelial cells; pyroptosis.

MeSH terms

  • Adult
  • Aged
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Cells, Cultured
  • Cornea / cytology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Epithelium, Corneal / metabolism*
  • Epithelium, Corneal / virology
  • Female
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Middle Aged
  • Phosphate-Binding Proteins / genetics
  • Phosphate-Binding Proteins / metabolism
  • Pyroptosis
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • GSDMD protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • Phosphate-Binding Proteins
  • Spike Glycoprotein, Coronavirus
  • Tumor Necrosis Factor-alpha
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2