A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/32989 http://dx.doi.org/10.1074/jbc.M110.124297 |
Resumo: | Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes called inflammasomes, culminating in caspase-1 activation, IL-1 beta/IL-18 secretion, and pyroptosis. Although both TLR5 and Naip5/Nlrc4 pathways cooperate to clear infections, little is known about the relative anti-pathogen effector mechanisms operating through each of them. Here we show that the cytosolic flagellin (FLA-BSDot) was able to activate iNOS, an enzyme previously associated with TLR5 pathway. Using Nlrc4- or Naip5-deficient macrophages, we found that both receptors are involved in iNOS activation by FLA-BSDot. Moreover, distinct from extracellular flagellin (FLA-BS), iNOS activation by intracellular flagellin is completely abrogated in the absence of caspase-1. Interestingly, IL-1 beta and IL-18 do not seem to be important for FLA-BSDot-mediated iNOS production. Together, our data defined an additional anti-pathogen effector mechanism operated through Naip5 and Nlrc4 inflammasomes and illustrated a novel signaling transduction pathway that activates iNOS. |
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Buzzo, Carina L.Campopiano, Julia C.Massis, Liliana M.Lage, Silvia L.Cassado, Alexandra A.Leme-Souza, RafaelCunha, Larissa D.Russo, MomtchiloZamboni, Dario S.Amarante-Mendes, Gustavo P.Bortoluci, Karina Ramalho [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)Inst Nacl Ciencia Tecnol2016-01-24T14:05:34Z2016-01-24T14:05:34Z2010-10-15Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 285, n. 42, p. 32087-32095, 2010.0021-9258http://repositorio.unifesp.br/handle/11600/32989http://dx.doi.org/10.1074/jbc.M110.12429710.1074/jbc.M110.124297WOS:000282683000022Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes called inflammasomes, culminating in caspase-1 activation, IL-1 beta/IL-18 secretion, and pyroptosis. Although both TLR5 and Naip5/Nlrc4 pathways cooperate to clear infections, little is known about the relative anti-pathogen effector mechanisms operating through each of them. Here we show that the cytosolic flagellin (FLA-BSDot) was able to activate iNOS, an enzyme previously associated with TLR5 pathway. Using Nlrc4- or Naip5-deficient macrophages, we found that both receptors are involved in iNOS activation by FLA-BSDot. Moreover, distinct from extracellular flagellin (FLA-BS), iNOS activation by intracellular flagellin is completely abrogated in the absence of caspase-1. Interestingly, IL-1 beta and IL-18 do not seem to be important for FLA-BSDot-mediated iNOS production. Together, our data defined an additional anti-pathogen effector mechanism operated through Naip5 and Nlrc4 inflammasomes and illustrated a novel signaling transduction pathway that activates iNOS.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Biol Sci, BR-04044010 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 São Paulo, BrazilUniv São Paulo, Dept Biol Celular, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, BrazilInst Nacl Ciencia Tecnol, Inst Invest Imunol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, BR-04044010 São Paulo, BrazilWeb of Science32087-32095engAmer Soc Biochemistry Molecular Biology IncJournal of Biological ChemistryA Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/329892022-09-27 09:59:57.387metadata only accessoai:repositorio.unifesp.br:11600/32989Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T12:59:57Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes |
title |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes |
spellingShingle |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes Buzzo, Carina L. |
title_short |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes |
title_full |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes |
title_fullStr |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes |
title_full_unstemmed |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes |
title_sort |
A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes |
author |
Buzzo, Carina L. |
author_facet |
Buzzo, Carina L. Campopiano, Julia C. Massis, Liliana M. Lage, Silvia L. Cassado, Alexandra A. Leme-Souza, Rafael Cunha, Larissa D. Russo, Momtchilo Zamboni, Dario S. Amarante-Mendes, Gustavo P. Bortoluci, Karina Ramalho [UNIFESP] |
author_role |
author |
author2 |
Campopiano, Julia C. Massis, Liliana M. Lage, Silvia L. Cassado, Alexandra A. Leme-Souza, Rafael Cunha, Larissa D. Russo, Momtchilo Zamboni, Dario S. Amarante-Mendes, Gustavo P. Bortoluci, Karina Ramalho [UNIFESP] |
author2_role |
author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade de São Paulo (USP) Inst Nacl Ciencia Tecnol |
dc.contributor.author.fl_str_mv |
Buzzo, Carina L. Campopiano, Julia C. Massis, Liliana M. Lage, Silvia L. Cassado, Alexandra A. Leme-Souza, Rafael Cunha, Larissa D. Russo, Momtchilo Zamboni, Dario S. Amarante-Mendes, Gustavo P. Bortoluci, Karina Ramalho [UNIFESP] |
description |
Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes called inflammasomes, culminating in caspase-1 activation, IL-1 beta/IL-18 secretion, and pyroptosis. Although both TLR5 and Naip5/Nlrc4 pathways cooperate to clear infections, little is known about the relative anti-pathogen effector mechanisms operating through each of them. Here we show that the cytosolic flagellin (FLA-BSDot) was able to activate iNOS, an enzyme previously associated with TLR5 pathway. Using Nlrc4- or Naip5-deficient macrophages, we found that both receptors are involved in iNOS activation by FLA-BSDot. Moreover, distinct from extracellular flagellin (FLA-BS), iNOS activation by intracellular flagellin is completely abrogated in the absence of caspase-1. Interestingly, IL-1 beta and IL-18 do not seem to be important for FLA-BSDot-mediated iNOS production. Together, our data defined an additional anti-pathogen effector mechanism operated through Naip5 and Nlrc4 inflammasomes and illustrated a novel signaling transduction pathway that activates iNOS. |
publishDate |
2010 |
dc.date.issued.fl_str_mv |
2010-10-15 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:05:34Z |
dc.date.available.fl_str_mv |
2016-01-24T14:05:34Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 285, n. 42, p. 32087-32095, 2010. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/32989 http://dx.doi.org/10.1074/jbc.M110.124297 |
dc.identifier.issn.none.fl_str_mv |
0021-9258 |
dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M110.124297 |
dc.identifier.wos.none.fl_str_mv |
WOS:000282683000022 |
identifier_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 285, n. 42, p. 32087-32095, 2010. 0021-9258 10.1074/jbc.M110.124297 WOS:000282683000022 |
url |
http://repositorio.unifesp.br/handle/11600/32989 http://dx.doi.org/10.1074/jbc.M110.124297 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Biological Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
32087-32095 |
dc.publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
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 |
|
_version_ |
1802764165792661504 |