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Synergism of TNF-α and IFN-ß triggers human airway epithelial cells death by apoptosis and pyroptosis.
Sun, Rui; Jiang, Kaimin; Zeng, Chengyue; Zhu, Rui; Chu, Hanyu; Liu, Huiyong; Du, Jingchun.
  • Sun R; Department of Clinical Immunology, Kingmed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
  • Jiang K; Department of Clinical Immunology, Kingmed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
  • Zeng C; Department of Clinical Immunology, Kingmed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
  • Zhu R; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
  • Chu H; Department of Clinical Immunology, Kingmed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
  • Liu H; Department of Clinical Immunology, Kingmed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
  • Du J; Department of Clinical Immunology, Kingmed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510182, China; Guangzhou Key Laboratory of Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Mol Immunol ; 153: 160-169, 2023 01.
Article in English | MEDLINE | ID: covidwho-2150304
ABSTRACT
Cytokine release syndrome, also called cytokine storm, could cause lung tissue damage, acute respiratory distress syndrome (ARDS) and even death during SARS-CoV-2 infection. However, the underlying mechanisms of cytokine storm still remain unknown. Among these cytokines, the function of TNF-α and type I IFNs especially deserved further investigation. Here, we first found that TNF-α and IFN-ß synergistically induced human airway epithelial cells BEAS-2B death. Mechanistically, the combination of TNF-α and IFN-ß led to the activation of caspase-8 and caspase-3, which initiated BEAS-2B apoptosis. The activated caspase-8 and caspase-3 could further induce the cleavage and activation of gasdermin D (GSDMD) and gasdermin E (GSDME), which finally resulted in pro-inflammatory pyroptosis. The knock-down of caspase-8 and caspase-3 could effectively block the activation of GSDMD and GSDME, and then the death of BEAS-2B induced by TNF-α and IFN-ß. In addition, pan-caspase inhibitor Z-VAD-FMK (ZVAD) and necrosulfonamide (NSA) could inhibit BEAS-2B death induced by TNF-α and IFN-ß. Overall, our work revealed one possible mechanism that cytokine storm causes airway epithelial cells (AECs) damage and ARDS. These results indicated that blocking TNF-α and IFN-ß-mediated AECs death may be a potential target to treat related viral infectious diseases, such as COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / COVID-19 Limits: Humans Language: English Journal: Mol Immunol Year: 2023 Document Type: Article Affiliation country: J.molimm.2022.12.002

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / COVID-19 Limits: Humans Language: English Journal: Mol Immunol Year: 2023 Document Type: Article Affiliation country: J.molimm.2022.12.002