The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.

<h4>Background</h4>Multiple sclerosis (MS) is a demyelinating and neuroinflammatory disease of the human central nervous system (CNS). The expression of kinins is increased in MS patients, but the underlying mechanisms by which the kinin receptor regulates MS development have not been el...

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Autores principales:	Rafael C Dutra, Daniela F P Leite, Allisson F Bento, Marianne N Manjavachi, Eliziane S Patrício, Cláudia P Figueiredo, João B Pesquero, João B Calixto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c2cc222a84b4e4b8ffac7b3db76244f
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spelling	oai:doaj.org-article:6c2cc222a84b4e4b8ffac7b3db76244f2021-11-18T07:33:44ZThe role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.1932-620310.1371/journal.pone.0027875https://doaj.org/article/6c2cc222a84b4e4b8ffac7b3db76244f2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22132157/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Multiple sclerosis (MS) is a demyelinating and neuroinflammatory disease of the human central nervous system (CNS). The expression of kinins is increased in MS patients, but the underlying mechanisms by which the kinin receptor regulates MS development have not been elucidated.<h4>Methodology/principal findings</h4>Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice by immunization with MOG(35-55) peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Here, we report that blockade of the B(1)R in the induction phase of EAE markedly suppressed its progression by interfering with the onset of the immune response. Furthermore, B(1)R antagonist suppressed the production/expression of antigen-specific T(H)1 and T(H)17 cytokines and transcription factors, both in the periphery and in the CNS. In the chronic phase of EAE, the blockade of B(1)R consistently impaired the clinical progression of EAE. Conversely, administration of the B(1)R agonist in the acute phase of EAE suppressed disease progression and inhibited the increase in permeability of the blood-brain barrier (BBB) and any further CNS inflammation. Of note, blockade of the B(2)R only showed a moderate impact on all of the studied parameters of EAE progression.<h4>Conclusions/significance</h4>Our results strongly suggest that kinin receptors, mainly the B(1)R subtype, play a dual role in EAE progression depending on the phase of treatment through the lymphocytes and glial cell-dependent pathways.Rafael C DutraDaniela F P LeiteAllisson F BentoMarianne N ManjavachiEliziane S PatrícioCláudia P FigueiredoJoão B PesqueroJoão B CalixtoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27875 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rafael C Dutra Daniela F P Leite Allisson F Bento Marianne N Manjavachi Eliziane S Patrício Cláudia P Figueiredo João B Pesquero João B Calixto The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.
description	<h4>Background</h4>Multiple sclerosis (MS) is a demyelinating and neuroinflammatory disease of the human central nervous system (CNS). The expression of kinins is increased in MS patients, but the underlying mechanisms by which the kinin receptor regulates MS development have not been elucidated.<h4>Methodology/principal findings</h4>Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice by immunization with MOG(35-55) peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Here, we report that blockade of the B(1)R in the induction phase of EAE markedly suppressed its progression by interfering with the onset of the immune response. Furthermore, B(1)R antagonist suppressed the production/expression of antigen-specific T(H)1 and T(H)17 cytokines and transcription factors, both in the periphery and in the CNS. In the chronic phase of EAE, the blockade of B(1)R consistently impaired the clinical progression of EAE. Conversely, administration of the B(1)R agonist in the acute phase of EAE suppressed disease progression and inhibited the increase in permeability of the blood-brain barrier (BBB) and any further CNS inflammation. Of note, blockade of the B(2)R only showed a moderate impact on all of the studied parameters of EAE progression.<h4>Conclusions/significance</h4>Our results strongly suggest that kinin receptors, mainly the B(1)R subtype, play a dual role in EAE progression depending on the phase of treatment through the lymphocytes and glial cell-dependent pathways.
format	article
author	Rafael C Dutra Daniela F P Leite Allisson F Bento Marianne N Manjavachi Eliziane S Patrício Cláudia P Figueiredo João B Pesquero João B Calixto
author_facet	Rafael C Dutra Daniela F P Leite Allisson F Bento Marianne N Manjavachi Eliziane S Patrício Cláudia P Figueiredo João B Pesquero João B Calixto
author_sort	Rafael C Dutra
title	The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.
title_short	The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.
title_full	The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.
title_fullStr	The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.
title_full_unstemmed	The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.
title_sort	role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/6c2cc222a84b4e4b8ffac7b3db76244f
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The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice.

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