Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      COVID-19* ; Influenza A Virus, H1N1 Subtype*/metabolism; Humans ; Inflammasomes/metabolism ; SARS-CoV-2 ; Interleukin-18 ; NF-kappa B/metabolism ; Angiotensin-Converting Enzyme 2 ; Autopsy ; Caspase 1/metabolism ; Lung/metabolism ; Cytokines/metabolism ; Biopsy ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
    • Abstract:
      The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease’s mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1β, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.
      Competing Interests: The authors declare no conflict of interest.
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    • Grant Information:
      BRDE-PUCPR; 304356/2018-2 National Council for Scientific and Technological Development
    • Contributed Indexing:
      Keywords: COVID-19; cytokine; immunohistochemistry; inflammasome; oxidative stress; pulmonary tissue; pyroptosis
    • Accession Number:
      0 (Inflammasomes)
      0 (Interleukin-18)
      0 (NF-kappa B)
      EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
      EC 3.4.22.36 (Caspase 1)
      0 (Cytokines)
      0 (NLR Family, Pyrin Domain-Containing 3 Protein)
    • Publication Date:
      Date Created: 20221111 Date Completed: 20221114 Latest Revision: 20230308
    • Publication Date:
      20231215
    • Accession Number:
      PMC9659061
    • Accession Number:
      10.3390/ijms232113033
    • Accession Number:
      36361818