Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31033 http://dx.doi.org/10.1186/1742-2094-5-49 |
Resumo: | Background: Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B(1) and B(2). Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis ( MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. the aim of the present study was to evaluate the relevance of B2 receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)(35-55)-induced EAE in mice.Methods: in order to evaluate the role of B2 receptor in the cerebral microvasculature we used wildtype (WT) and kinin B2 receptor knockout (B(2)(-/-)) mice subjected to MOG(35-55)-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B(2)(-/-) and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. the expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA.Results: Clinical parameters of disease were reduced in B(2)(-/-) mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B(2)(-/-) mice when compared to WT.Conclusion: Our results suggest that B(2) receptors have two major effects in the control of EAE severity: (i) B(2) regulates the expression of chemokines, including CCL2 and CCL5, and (ii) B(2) modulates leukocyte recruitment and inflammatory lesions in the CNS. |
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Santos, Adriana C. dosRoffe, EsterArantes, Rosa M. E.Juliano, Luiz [UNIFESP]Pesquero, Jorge L.Pesquero, João Bosco [UNIFESP]Bader, Michael [UNIFESP]Teixeira, Mauro M.Carvalho-Tavares, JulianaUniversidade Federal de Minas Gerais (UFMG)Universidade Federal de São Paulo (UNIFESP)Max Delbruck Ctr Mol Med2016-01-24T13:51:53Z2016-01-24T13:51:53Z2008-11-05Journal of Neuroinflammation. London: Biomed Central Ltd, v. 5, 10 p., 2008.1742-2094http://repositorio.unifesp.br/handle/11600/31033http://dx.doi.org/10.1186/1742-2094-5-49WOS000261437000001.pdf10.1186/1742-2094-5-49WOS:000261437000001Background: Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B(1) and B(2). Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis ( MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. the aim of the present study was to evaluate the relevance of B2 receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)(35-55)-induced EAE in mice.Methods: in order to evaluate the role of B2 receptor in the cerebral microvasculature we used wildtype (WT) and kinin B2 receptor knockout (B(2)(-/-)) mice subjected to MOG(35-55)-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B(2)(-/-) and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. the expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA.Results: Clinical parameters of disease were reduced in B(2)(-/-) mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B(2)(-/-) mice when compared to WT.Conclusion: Our results suggest that B(2) receptors have two major effects in the control of EAE severity: (i) B(2) regulates the expression of chemokines, including CCL2 and CCL5, and (ii) B(2) modulates leukocyte recruitment and inflammatory lesions in the CNS.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Dept Biochem & Immunol, Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Dept Pathol, Belo Horizonte, MG, BrazilEscola Paulista Med, BR-04023 São Paulo, BrazilMax Delbruck Ctr Mol Med, Berlin, GermanyEscola Paulista Med, BR-04023 São Paulo, BrazilWeb of Science10engBiomed Central LtdJournal of NeuroinflammationKinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000261437000001.pdfapplication/pdf428530${dspace.ui.url}/bitstream/11600/31033/1/WOS000261437000001.pdfbb194ab01e9b749da24b94463b063c66MD51open accessTEXTWOS000261437000001.pdf.txtWOS000261437000001.pdf.txtExtracted texttext/plain45055${dspace.ui.url}/bitstream/11600/31033/2/WOS000261437000001.pdf.txt97142eae2eb6f035c9db664e3405a8ccMD52open access11600/310332022-07-08 10:54:12.988open accessoai:repositorio.unifesp.br:11600/31033Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:21:20.749627Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice |
title |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice |
spellingShingle |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice Santos, Adriana C. dos |
title_short |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice |
title_full |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice |
title_fullStr |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice |
title_full_unstemmed |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice |
title_sort |
Kinin B(2) receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice |
author |
Santos, Adriana C. dos |
author_facet |
Santos, Adriana C. dos Roffe, Ester Arantes, Rosa M. E. Juliano, Luiz [UNIFESP] Pesquero, Jorge L. Pesquero, João Bosco [UNIFESP] Bader, Michael [UNIFESP] Teixeira, Mauro M. Carvalho-Tavares, Juliana |
author_role |
author |
author2 |
Roffe, Ester Arantes, Rosa M. E. Juliano, Luiz [UNIFESP] Pesquero, Jorge L. Pesquero, João Bosco [UNIFESP] Bader, Michael [UNIFESP] Teixeira, Mauro M. Carvalho-Tavares, Juliana |
author2_role |
author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de Minas Gerais (UFMG) Universidade Federal de São Paulo (UNIFESP) Max Delbruck Ctr Mol Med |
dc.contributor.author.fl_str_mv |
Santos, Adriana C. dos Roffe, Ester Arantes, Rosa M. E. Juliano, Luiz [UNIFESP] Pesquero, Jorge L. Pesquero, João Bosco [UNIFESP] Bader, Michael [UNIFESP] Teixeira, Mauro M. Carvalho-Tavares, Juliana |
description |
Background: Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B(1) and B(2). Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis ( MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. the aim of the present study was to evaluate the relevance of B2 receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)(35-55)-induced EAE in mice.Methods: in order to evaluate the role of B2 receptor in the cerebral microvasculature we used wildtype (WT) and kinin B2 receptor knockout (B(2)(-/-)) mice subjected to MOG(35-55)-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B(2)(-/-) and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. the expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA.Results: Clinical parameters of disease were reduced in B(2)(-/-) mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B(2)(-/-) mice when compared to WT.Conclusion: Our results suggest that B(2) receptors have two major effects in the control of EAE severity: (i) B(2) regulates the expression of chemokines, including CCL2 and CCL5, and (ii) B(2) modulates leukocyte recruitment and inflammatory lesions in the CNS. |
publishDate |
2008 |
dc.date.issued.fl_str_mv |
2008-11-05 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:51:53Z |
dc.date.available.fl_str_mv |
2016-01-24T13:51:53Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Journal of Neuroinflammation. London: Biomed Central Ltd, v. 5, 10 p., 2008. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31033 http://dx.doi.org/10.1186/1742-2094-5-49 |
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1742-2094 |
dc.identifier.file.none.fl_str_mv |
WOS000261437000001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/1742-2094-5-49 |
dc.identifier.wos.none.fl_str_mv |
WOS:000261437000001 |
identifier_str_mv |
Journal of Neuroinflammation. London: Biomed Central Ltd, v. 5, 10 p., 2008. 1742-2094 WOS000261437000001.pdf 10.1186/1742-2094-5-49 WOS:000261437000001 |
url |
http://repositorio.unifesp.br/handle/11600/31033 http://dx.doi.org/10.1186/1742-2094-5-49 |
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eng |
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Journal of Neuroinflammation |
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Biomed Central Ltd |
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Biomed Central Ltd |
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