Is serum amyloid A an endogenous TLR4 agonist?

Detalhes bibliográficos
Autor(a) principal: Sandri, Silvana
Data de Publicação: 2008
Outros Autores: Rodriguez, Dunia, Gomes, Eliane, Monteiro, Hugo Pequeno [UNIFESP], Russo, Momtchilo, Campa, Ana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1189/jlb.0407203
http://repositorio.unifesp.br/handle/11600/30621
Resumo: Serum amyloid A (SAA), a classical acute-phase protein, is produced predominantly by hepatocytes in response to injury, infection, and inflammation. It has been shown that SAA primes leukocytes and induces the expression and release of proinflammatory cytokines. Here, we report that SAA induces NO production by murine peritoneal macrophages. Using specific inhibitors, we showed that NO production was dependent on inducible NO synthase thorough the activation of ERK1/2 and p38 MAPKs. Moreover, SAA activity was decreased after proteolysis but not with polymyxin B, a lipid A antagonist. Finally, we found that NO production was dependent on functional TLR4, a receptor complex associated with innate immunity. Macrophages from C3H/HeJ and C57BL/10ScCr mice lacking a functional TLR4 did not respond to SAA stimulation. in conclusion, our study makes a novel observation that SAA might be an endogenous agonist for the TLR4 complex on macrophages. the contribution of this finding in amplifying innate immunity during the inflammatory process is discussed.
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spelling Is serum amyloid A an endogenous TLR4 agonist?toll like receptorsmacrophagesnitric oxide (NO)Serum amyloid A (SAA), a classical acute-phase protein, is produced predominantly by hepatocytes in response to injury, infection, and inflammation. It has been shown that SAA primes leukocytes and induces the expression and release of proinflammatory cytokines. Here, we report that SAA induces NO production by murine peritoneal macrophages. Using specific inhibitors, we showed that NO production was dependent on inducible NO synthase thorough the activation of ERK1/2 and p38 MAPKs. Moreover, SAA activity was decreased after proteolysis but not with polymyxin B, a lipid A antagonist. Finally, we found that NO production was dependent on functional TLR4, a receptor complex associated with innate immunity. Macrophages from C3H/HeJ and C57BL/10ScCr mice lacking a functional TLR4 did not respond to SAA stimulation. in conclusion, our study makes a novel observation that SAA might be an endogenous agonist for the TLR4 complex on macrophages. the contribution of this finding in amplifying innate immunity during the inflammatory process is discussed.Univ São Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 São Paulo, BrazilUniv São Paulo, Dept Clin Anal & Toxicol, Fac Pharmaceut Sci, BR-05508000 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem Mol Biol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem Mol Biol, São Paulo, BrazilWeb of ScienceFederation Amer Soc Exp BiolUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Sandri, SilvanaRodriguez, DuniaGomes, ElianeMonteiro, Hugo Pequeno [UNIFESP]Russo, MomtchiloCampa, Ana2016-01-24T13:49:46Z2016-01-24T13:49:46Z2008-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion1174-1180http://dx.doi.org/10.1189/jlb.0407203Journal of Leukocyte Biology. Bethesda: Federation Amer Soc Exp Biol, v. 83, n. 5, p. 1174-1180, 2008.10.1189/jlb.04072030741-5400http://repositorio.unifesp.br/handle/11600/30621WOS:000258019500012engJournal of Leukocyte Biologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-10-14T13:51:15Zoai:repositorio.unifesp.br/:11600/30621Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-10-14T13:51:15Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Is serum amyloid A an endogenous TLR4 agonist?
title Is serum amyloid A an endogenous TLR4 agonist?
spellingShingle Is serum amyloid A an endogenous TLR4 agonist?
Sandri, Silvana
toll like receptors
macrophages
nitric oxide (NO)
title_short Is serum amyloid A an endogenous TLR4 agonist?
title_full Is serum amyloid A an endogenous TLR4 agonist?
title_fullStr Is serum amyloid A an endogenous TLR4 agonist?
title_full_unstemmed Is serum amyloid A an endogenous TLR4 agonist?
title_sort Is serum amyloid A an endogenous TLR4 agonist?
author Sandri, Silvana
author_facet Sandri, Silvana
Rodriguez, Dunia
Gomes, Eliane
Monteiro, Hugo Pequeno [UNIFESP]
Russo, Momtchilo
Campa, Ana
author_role author
author2 Rodriguez, Dunia
Gomes, Eliane
Monteiro, Hugo Pequeno [UNIFESP]
Russo, Momtchilo
Campa, Ana
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Sandri, Silvana
Rodriguez, Dunia
Gomes, Eliane
Monteiro, Hugo Pequeno [UNIFESP]
Russo, Momtchilo
Campa, Ana
dc.subject.por.fl_str_mv toll like receptors
macrophages
nitric oxide (NO)
topic toll like receptors
macrophages
nitric oxide (NO)
description Serum amyloid A (SAA), a classical acute-phase protein, is produced predominantly by hepatocytes in response to injury, infection, and inflammation. It has been shown that SAA primes leukocytes and induces the expression and release of proinflammatory cytokines. Here, we report that SAA induces NO production by murine peritoneal macrophages. Using specific inhibitors, we showed that NO production was dependent on inducible NO synthase thorough the activation of ERK1/2 and p38 MAPKs. Moreover, SAA activity was decreased after proteolysis but not with polymyxin B, a lipid A antagonist. Finally, we found that NO production was dependent on functional TLR4, a receptor complex associated with innate immunity. Macrophages from C3H/HeJ and C57BL/10ScCr mice lacking a functional TLR4 did not respond to SAA stimulation. in conclusion, our study makes a novel observation that SAA might be an endogenous agonist for the TLR4 complex on macrophages. the contribution of this finding in amplifying innate immunity during the inflammatory process is discussed.
publishDate 2008
dc.date.none.fl_str_mv 2008-05-01
2016-01-24T13:49:46Z
2016-01-24T13:49:46Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1189/jlb.0407203
Journal of Leukocyte Biology. Bethesda: Federation Amer Soc Exp Biol, v. 83, n. 5, p. 1174-1180, 2008.
10.1189/jlb.0407203
0741-5400
http://repositorio.unifesp.br/handle/11600/30621
WOS:000258019500012
url http://dx.doi.org/10.1189/jlb.0407203
http://repositorio.unifesp.br/handle/11600/30621
identifier_str_mv Journal of Leukocyte Biology. Bethesda: Federation Amer Soc Exp Biol, v. 83, n. 5, p. 1174-1180, 2008.
10.1189/jlb.0407203
0741-5400
WOS:000258019500012
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Leukocyte Biology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1174-1180
dc.publisher.none.fl_str_mv Federation Amer Soc Exp Biol
publisher.none.fl_str_mv Federation Amer Soc Exp Biol
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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