Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke

Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic modality used for various inflammatory diseases. The objective of this study is to investigate dynamic r...

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Main Authors:	Yang-Wei Fann, D, Lee, S-Y, Manzanero, S, Tang, S-C, Gelderblom, M, Chunduri, P, Bernreuther, C, Glatzel, M, Cheng, Y-L, Thundyil, J, Widiapradja, A, Lok, K-Z, Foo, S L, Wang, Y-C, Li, Y-I, Drummond, G R, Basta, M, Magnus, T, Jo, D-G, Mattson, M P, Sobey, C G, Arumugam, T V
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789184/

id	pubmed-3789184
recordtype	oai_dc
spelling	pubmed-37891842013-10-18 Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke Yang-Wei Fann, D Lee, S-Y Manzanero, S Tang, S-C Gelderblom, M Chunduri, P Bernreuther, C Glatzel, M Cheng, Y-L Thundyil, J Widiapradja, A Lok, K-Z Foo, S L Wang, Y-C Li, Y-I Drummond, G R Basta, M Magnus, T Jo, D-G Mattson, M P Sobey, C G Arumugam, T V Original Article Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen–glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1β and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1β and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity. Nature Publishing Group 2013-09 2013-09-05 /pmc/articles/PMC3789184/ /pubmed/24008734 http://dx.doi.org/10.1038/cddis.2013.326 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yang-Wei Fann, D Lee, S-Y Manzanero, S Tang, S-C Gelderblom, M Chunduri, P Bernreuther, C Glatzel, M Cheng, Y-L Thundyil, J Widiapradja, A Lok, K-Z Foo, S L Wang, Y-C Li, Y-I Drummond, G R Basta, M Magnus, T Jo, D-G Mattson, M P Sobey, C G Arumugam, T V
spellingShingle	Yang-Wei Fann, D Lee, S-Y Manzanero, S Tang, S-C Gelderblom, M Chunduri, P Bernreuther, C Glatzel, M Cheng, Y-L Thundyil, J Widiapradja, A Lok, K-Z Foo, S L Wang, Y-C Li, Y-I Drummond, G R Basta, M Magnus, T Jo, D-G Mattson, M P Sobey, C G Arumugam, T V Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke
author_facet	Yang-Wei Fann, D Lee, S-Y Manzanero, S Tang, S-C Gelderblom, M Chunduri, P Bernreuther, C Glatzel, M Cheng, Y-L Thundyil, J Widiapradja, A Lok, K-Z Foo, S L Wang, Y-C Li, Y-I Drummond, G R Basta, M Magnus, T Jo, D-G Mattson, M P Sobey, C G Arumugam, T V
author_sort	Yang-Wei Fann, D
title	Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke
title_short	Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke
title_full	Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke
title_fullStr	Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke
title_full_unstemmed	Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke
title_sort	intravenous immunoglobulin suppresses nlrp1 and nlrp3 inflammasome-mediated neuronal death in ischemic stroke
description	Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen–glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1β and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1β and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789184/
_version_	1612015895211671552

Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke

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