دورية أكاديمية
أعرض في EDS

Shiga Toxin/Lipopolysaccharide Activates Caspase-4 and Gasdermin D to Trigger Mitochondrial Reactive Oxygen Species Upstream of the NLRP3 Inflammasome.

التفاصيل البيبلوغرافية
العنوان: Shiga Toxin/Lipopolysaccharide Activates Caspase-4 and Gasdermin D to Trigger Mitochondrial Reactive Oxygen Species Upstream of the NLRP3 Inflammasome.
المؤلفون: Platnich JM; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Chung H; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Lau A; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Sandall CF; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada., Bondzi-Simpson A; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Chen HM; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada., Komada T; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Trotman-Grant AC; Department of Immunology, University of Toronto, Toronto, ON, Canada., Brandelli JR; Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Chun J; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Beck PL; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Philpott DJ; Department of Immunology, University of Toronto, Toronto, ON, Canada., Girardin SE; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Ho M; Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Johnson RP; Public Health Agency of Canada, National Microbiology Laboratory, Guelph, ON, Canada., MacDonald JA; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada., Armstrong GD; Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada., Muruve DA; Department of Medicine, University of Calgary, Calgary, AB, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada. Electronic address: dmuruve@ucalgary.ca.
المصدر: Cell reports [Cell Rep] 2018 Nov 06; Vol. 25 (6), pp. 1525-1536.e7.
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, Initiator/*metabolism , Inflammasomes/*metabolism , Lipopolysaccharides/*pharmacology , Mitochondria/*metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism , Neoplasm Proteins/*metabolism , Reactive Oxygen Species/*metabolism , Shiga Toxin/*pharmacology, Animals ; Cell Line ; Enzyme Activation/drug effects ; Humans ; Intracellular Signaling Peptides and Proteins ; Macrophages/drug effects ; Macrophages/metabolism ; Mice, Inbred C57BL ; Mitochondria/drug effects ; Phosphate-Binding Proteins ; Pyroptosis/drug effects
مستخلص: The non-canonical caspase-4 and canonical NLRP3 inflammasomes are both activated by intracellular lipopolysaccharide (LPS), but the crosstalk between these two pathways remains unclear. Shiga toxin 2 (Stx2)/LPS complex, from pathogenic enterohemorrhagic Escherichia coli, activates caspase-4, gasdermin D (GSDMD), and the NLRP3 inflammasome in human THP-1 macrophages, but not mouse macrophages that lack the Stx receptor CD77. Stx2/LPS-mediated IL-1β secretion and pyroptosis are dependent on mitochondrial reactive oxygen species (ROS) downstream of the non-canonical caspase-4 inflammasome and cleaved GSDMD, which is enriched at the mitochondria. Blockade of caspase-4 activation and ROS generation as well as GSDMD deficiency significantly reduces Stx2/LPS-induced IL-1β production and pyroptosis. The NLRP3 inflammasome plays a significant role in amplifying Stx2/LPS-induced GSDMD cleavage and pyroptosis, with significant reduction of these responses in NLRP3-deficient THP-1 cells. Together, these data show that Stx2/LPS complex activates the non-canonical inflammasome and mitochondrial ROS upstream of the NLRP3 inflammasome to promote cytokine maturation and pyroptosis.
(Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: NLRP3; Shiga toxin; caspase-4; enterohemorrhagic Escherichia coli; gasdermin D; inflammasome; macrophages
المشرفين على المادة: 0 (GSDMD protein, human)
0 (Inflammasomes)
0 (Intracellular Signaling Peptides and Proteins)
0 (Lipopolysaccharides)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Neoplasm Proteins)
0 (Phosphate-Binding Proteins)
0 (Reactive Oxygen Species)
75757-64-1 (Shiga Toxin)
EC 3.4.22.- (CASP4 protein, human)
EC 3.4.22.- (Caspases, Initiator)
تواريخ الأحداث: Date Created: 20181108 Date Completed: 20191210 Latest Revision: 20201209
رمز التحديث: 20231215
DOI: 10.1016/j.celrep.2018.09.071
PMID: 30404007
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2018.09.071