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TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models

BACKGROUND: The innate immune response plays an important role in the pathogenesis of intracerebral hemorrhage (ICH). Recent studies have shown that Toll-like receptor 2 (TLR2) is involved in the innate immune response in various neurological diseases, yet neither its role in ICH nor the mechanisms...

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Autores principales: Min, Hyunjung, Hong, Jinpyo, Cho, Ik-Hyun, Jang, Yong Ho, Lee, Hyunkyoung, Kim, Dongwoon, Yu, Seong-Woon, Lee, Soojin, Lee, Sung Joong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397689/
https://www.ncbi.nlm.nih.gov/pubmed/25879213
http://dx.doi.org/10.1186/s13041-015-0116-z
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author Min, Hyunjung
Hong, Jinpyo
Cho, Ik-Hyun
Jang, Yong Ho
Lee, Hyunkyoung
Kim, Dongwoon
Yu, Seong-Woon
Lee, Soojin
Lee, Sung Joong
author_facet Min, Hyunjung
Hong, Jinpyo
Cho, Ik-Hyun
Jang, Yong Ho
Lee, Hyunkyoung
Kim, Dongwoon
Yu, Seong-Woon
Lee, Soojin
Lee, Sung Joong
author_sort Min, Hyunjung
collection PubMed
description BACKGROUND: The innate immune response plays an important role in the pathogenesis of intracerebral hemorrhage (ICH). Recent studies have shown that Toll-like receptor 2 (TLR2) is involved in the innate immune response in various neurological diseases, yet neither its role in ICH nor the mechanisms by which it functions have yet been elucidated. We examined these in this study using a collagenase-induced mouse ICH model with TLR2 knock-out (KO) mice. RESULTS: TLR2 expression was upregulated in the ipsilateral hemorrhagic tissues of the collagenase-injected mice. Brain injury volume and neurological deficits following ICH were reduced in TLR2 KO mice compared to wild-type (WT) control mice. Heterologous blood-transfer experiments show that TLR2 signaling in brain-resident cells, but not leukocytes, contributes to the injury. In our study to elucidate underlying mechanisms, we found that damage to blood–brain barrier (BBB) integrity following ICH was attenuated in TLR2 KO mice compared to WT mice, which may be due to reduced matrix metalloproteinase-9 (MMP9) activation in astrocytes. The reduced BBB damage accompanies decreased neutrophil infiltration and proinflammatory gene expression in the injured brain parenchyma, which may account for the attenuated brain damage in TLR2 KO mice after ICH. CONCLUSIONS: TLR2 plays a detrimental role in ICH-induced brain damage by activating MMP9 in astrocytes, compromising BBB, and enhancing neutrophils infiltration and proinflammatory gene expression.
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spelling pubmed-43976892015-04-16 TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models Min, Hyunjung Hong, Jinpyo Cho, Ik-Hyun Jang, Yong Ho Lee, Hyunkyoung Kim, Dongwoon Yu, Seong-Woon Lee, Soojin Lee, Sung Joong Mol Brain Research BACKGROUND: The innate immune response plays an important role in the pathogenesis of intracerebral hemorrhage (ICH). Recent studies have shown that Toll-like receptor 2 (TLR2) is involved in the innate immune response in various neurological diseases, yet neither its role in ICH nor the mechanisms by which it functions have yet been elucidated. We examined these in this study using a collagenase-induced mouse ICH model with TLR2 knock-out (KO) mice. RESULTS: TLR2 expression was upregulated in the ipsilateral hemorrhagic tissues of the collagenase-injected mice. Brain injury volume and neurological deficits following ICH were reduced in TLR2 KO mice compared to wild-type (WT) control mice. Heterologous blood-transfer experiments show that TLR2 signaling in brain-resident cells, but not leukocytes, contributes to the injury. In our study to elucidate underlying mechanisms, we found that damage to blood–brain barrier (BBB) integrity following ICH was attenuated in TLR2 KO mice compared to WT mice, which may be due to reduced matrix metalloproteinase-9 (MMP9) activation in astrocytes. The reduced BBB damage accompanies decreased neutrophil infiltration and proinflammatory gene expression in the injured brain parenchyma, which may account for the attenuated brain damage in TLR2 KO mice after ICH. CONCLUSIONS: TLR2 plays a detrimental role in ICH-induced brain damage by activating MMP9 in astrocytes, compromising BBB, and enhancing neutrophils infiltration and proinflammatory gene expression. BioMed Central 2015-04-10 /pmc/articles/PMC4397689/ /pubmed/25879213 http://dx.doi.org/10.1186/s13041-015-0116-z Text en © Min et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Min, Hyunjung
Hong, Jinpyo
Cho, Ik-Hyun
Jang, Yong Ho
Lee, Hyunkyoung
Kim, Dongwoon
Yu, Seong-Woon
Lee, Soojin
Lee, Sung Joong
TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models
title TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models
title_full TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models
title_fullStr TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models
title_full_unstemmed TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models
title_short TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models
title_sort tlr2-induced astrocyte mmp9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397689/
https://www.ncbi.nlm.nih.gov/pubmed/25879213
http://dx.doi.org/10.1186/s13041-015-0116-z
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