Necroptosis in alveolar epithelial cells drives lung inflammation and injury caused by SARS-CoV-2 infection.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-260X (Electronic) Linking ISSN: 09254439 NLM ISO Abbreviation: Biochim Biophys Acta Mol Basis Dis Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
      COVID-19*/pathology ; COVID-19*/immunology ; COVID-19*/metabolism ; COVID-19*/virology ; COVID-19*/complications ; Necroptosis* ; SARS-CoV-2* ; Alveolar Epithelial Cells*/metabolism ; Alveolar Epithelial Cells*/pathology ; Alveolar Epithelial Cells*/virology; Animals ; Humans ; Mice ; HMGB1 Protein/metabolism ; HMGB1 Protein/genetics ; Lung Injury/pathology ; Lung Injury/virology ; Lung Injury/immunology ; Lung Injury/metabolism ; Male ; Disease Models, Animal ; Female ; Mice, Inbred C57BL ; fas Receptor/metabolism ; fas Receptor/genetics ; Mice, Knockout ; Pneumonia/pathology ; Pneumonia/virology ; Pneumonia/metabolism ; Pneumonia/immunology ; Middle Aged ; Imidazoles ; Indoles
    • Abstract:
      COVID-19, caused by SARS-CoV-2 infection, results in irreversible or fatal lung injury. We assumed that necroptosis of virus-infected alveolar epithelial cells (AEC) could promote local inflammation and further lung injury in COVID-19. Since CD8+ lymphocytes induced AEC cell death via cytotoxic molecules such as FAS ligands, we examined the involvement of FAS-mediated cell death in COVID-19 patients and murine COVID-19 model. We identified the occurrence of necroptosis and subsequent release of HMGB1 in the admitted patients with COVID-19. In the mouse model of COVID-19, lung inflammation and injury were attenuated in Fas-deficient mice compared to Fas-intact mice. The infection enhanced Type I interferon-inducible genes in both groups, while inflammasome-associated genes were specifically upregulated in Fas-intact mice. The treatment with necroptosis inhibitor, Nec1s, improved survival rate, lung injury, and systemic inflammation. SARS-CoV-2 induced necroptosis causes cytokine induction and lung damage, and its inhibition could be a novel therapeutic strategy for COVID-19.
      Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shinsuke Yasuda reports a relationship with AbbVie Inc. that includes: funding grants and speaking and lecture fees. Shinsuke Yasuda reports a relationship with Asahi Kasei Pharma Corporation that includes: funding grants and speaking and lecture fees. Shinsuke Yasuda reports a relationship with Chugai Pharmaceutical Co Ltd. that includes: funding grants and speaking and lecture fees. Shinsuke Yasuda reports a relationship with CSL Behring that includes: funding grants. Shinsuke Yasuda reports a relationship with Eisai Inc. that includes: funding grants and speaking and lecture fees. Shinsuke Yasuda reports a relationship with ImmunoForge that includes: funding grants. Shinsuke Yasuda reports a relationship with Mitsubishi Tanabe Pharma Corporation that includes: funding grants and speaking and lecture fees. Shinsuke Yasuda reports a relationship with Ono Pharmaceutical Co Ltd. that includes: funding grants and speaking and lecture fees. Shinsuke Yasuda reports a relationship with Eli Lilly that includes: speaking and lecture fees. Shinsuke Yasuda reports a relationship with GlaxoSmithKline that includes: speaking and lecture fees. Shinsuke Yasuda reports a relationship with Pfizer Inc. that includes: speaking and lecture fees. Tadashi Hosoya reports a relationship with Sony Corporation that includes: funding grants. Tadashi Hosoya reports a relationship with Terumo life science foundation that includes: funding grants. Mari Kamiya reports a relationship with GlaxoSmithKline that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Admitted patient's data; COVID-19; Fas-mediated cell death; NECROPTOSIS; RIPK1 inhibitor
    • Accession Number:
      0 (HMGB1 Protein)
      0 (fas Receptor)
      0 (necrostatin-1)
      0 (Imidazoles)
      0 (Indoles)
    • Publication Date:
      Date Created: 20240818 Date Completed: 20240918 Latest Revision: 20240918
    • Publication Date:
      20240919
    • Accession Number:
      10.1016/j.bbadis.2024.167472
    • Accession Number:
      39154794