دورية أكاديمية
An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages.
العنوان: | An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages. |
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المؤلفون: | de Vasconcelos NM; Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium; VIB Center for Inflammation Research, 9052 Ghent, Belgium., Van Opdenbosch N; Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium; VIB Center for Inflammation Research, 9052 Ghent, Belgium; Janssen Immunosciences, World Without Disease Accelerator, Pharmaceutical Companies of Johnson & Johnson, Beerse 2340, Belgium., Van Gorp H; Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium; VIB Center for Inflammation Research, 9052 Ghent, Belgium., Martín-Pérez R; Janssen Immunosciences, World Without Disease Accelerator, Pharmaceutical Companies of Johnson & Johnson, Beerse 2340, Belgium., Zecchin A; Janssen Immunosciences, World Without Disease Accelerator, Pharmaceutical Companies of Johnson & Johnson, Beerse 2340, Belgium., Vandenabeele P; VIB Center for Inflammation Research, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent 9052, Belgium; Methusalem program, Ghent University, Ghent 9052, Belgium., Lamkanfi M; Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium; VIB Center for Inflammation Research, 9052 Ghent, Belgium; Janssen Immunosciences, World Without Disease Accelerator, Pharmaceutical Companies of Johnson & Johnson, Beerse 2340, Belgium. Electronic address: mohamed.lamkanfi@ugent.be. |
المصدر: | Cell reports [Cell Rep] 2020 Jul 28; Vol. 32 (4), pp. 107959. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
مواضيع طبية MeSH: | Caspases/*metabolism , Macrophages/*metabolism , Pyroptosis/*physiology, Animals ; Apoptosis/physiology ; Apoptosis Regulatory Proteins/metabolism ; Caspase 1/metabolism ; Caspase 1/physiology ; Caspase 3/metabolism ; Caspase 7/metabolism ; Caspase 8/metabolism ; Caspase 8/physiology ; Cell Death ; Cell Membrane/metabolism ; Female ; Inflammasomes/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phosphate-Binding Proteins/metabolism |
مستخلص: | Pyroptosis has emerged as a key mechanism by which inflammasomes promote host defense against microbial pathogens and sterile inflammation. Gasdermin D (GSDMD)-mediated cell lysis is a hallmark of pyroptosis, but our understanding of cell death signaling during pyroptosis is fragmented. Here, we show that independently of GSDMD-mediated plasma membrane permeabilization, inflammasome receptors engage caspase-1 and caspase-8, both of which redundantly promote activation of apoptotic executioner caspase-3 and caspase-7 in pyroptotic macrophages. Impaired GSDMD pore formation downstream of caspase-1 and caspase-8 activation suffices to unmask the apoptotic phenotype of pyroptotic macrophages. Combined inactivation of initiator caspase-1 and caspase-8, or executioner caspase-3 and caspase-7, is required to abolish inflammasome-induced DEVDase activity during pyroptosis and in apoptotic Gsdmd -/- cells. Collectively, these results unveil a robust apoptotic caspase network that is activated in parallel to GSDMD-mediated plasma membrane permeabilization and safeguards cell death induction in pyroptotic macrophages. Competing Interests: Declaration of Interests N.V.O., R.M.-P., A.Z., and M.L. are/were employees of Janssen Pharmaceutica. The authors declare no other competing interests. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | 683144 International ERC_ European Research Council |
فهرسة مساهمة: | Keywords: GSDMD; apoptosis; caspase-1; caspase-3; caspase-7; caspase-8; inflammasome; pyroptosis |
المشرفين على المادة: | 0 (Apoptosis Regulatory Proteins) 0 (Gsdmd protein, mouse) 0 (Inflammasomes) 0 (Intracellular Signaling Peptides and Proteins) 0 (Phosphate-Binding Proteins) EC 3.4.22.- (Casp8 protein, mouse) EC 3.4.22.- (Caspase 3) EC 3.4.22.- (Caspase 7) EC 3.4.22.- (Caspase 8) EC 3.4.22.- (Caspases) EC 3.4.22.36 (Casp1 protein, mouse) EC 3.4.22.36 (Caspase 1) |
تواريخ الأحداث: | Date Created: 20200730 Date Completed: 20210510 Latest Revision: 20210924 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7408007 |
DOI: | 10.1016/j.celrep.2020.107959 |
PMID: | 32726624 |
قاعدة البيانات: | MEDLINE |
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