Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model

Detalhes bibliográficos
Autor(a) principal: Souza, Joao A.C. [UNESP]
Data de Publicação: 2016
Outros Autores: Medeiros, Marcell C. [UNESP], Rocha, Fernanda R.G. [UNESP], De Aquino, Sabrina G. [UNESP], Ávila-Campos, Mario J., Spolidorio, Luis C. [UNESP], Zamboni, Dario S., Graves, Dana T., Rossa, Carlos [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1177/1753425916666652
http://hdl.handle.net/11449/173651
Resumo: NOD2 is a member of the NLR family of proteins that participate in the activation of the innate immune response. RIP2 is a downstream kinase activated by both NOD1 and NOD2. There is scarcity of information regarding the relevance of NOD2 in periodontitis, a chronic inflammatory condition characterized by inflammatory bone resorption. We used NOD2-KO and RIP2-KO mice in a model of microbial-induced periodontitis. Heat-killed Aggregatibacter actinomycetemcomitans was injected in the gingival tissues three times/wk for 4 wk. Bone resorption was assessed by μCT analysis; osteoclasts were identified by immunohistochemical staining for TRAP and inflammation was assessed using a severity score system in H/E-stained sections. In vitro studies using primary macrophages assessed the response macrophages using qPCR-based array and multi-ligand ELISA. Bone resorption and osteoclastogenesis were significantly reduced in NOD2-KO mice. Severity of inflammation was not affected. qPCR-focused arrays and multi-ligand ELISA showed that expression of pro-inflammatory mediators was reduced in NOD2- and RIP2-deficient cells. RANKL-induced osteoclastogenesis was impaired in NOD2- and RIP2-deficient macrophages. We conclude that NOD2 is important for osteoclast differentiation and inflammatory bone resorption in vivo and also for the macrophage response to Gram-negative bacteria.
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spelling Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease modelBone resorptioninflammationinnate immunitymacrophagesNOD2 signaling adaptor proteinNOD2 is a member of the NLR family of proteins that participate in the activation of the innate immune response. RIP2 is a downstream kinase activated by both NOD1 and NOD2. There is scarcity of information regarding the relevance of NOD2 in periodontitis, a chronic inflammatory condition characterized by inflammatory bone resorption. We used NOD2-KO and RIP2-KO mice in a model of microbial-induced periodontitis. Heat-killed Aggregatibacter actinomycetemcomitans was injected in the gingival tissues three times/wk for 4 wk. Bone resorption was assessed by μCT analysis; osteoclasts were identified by immunohistochemical staining for TRAP and inflammation was assessed using a severity score system in H/E-stained sections. In vitro studies using primary macrophages assessed the response macrophages using qPCR-based array and multi-ligand ELISA. Bone resorption and osteoclastogenesis were significantly reduced in NOD2-KO mice. Severity of inflammation was not affected. qPCR-focused arrays and multi-ligand ELISA showed that expression of pro-inflammatory mediators was reduced in NOD2- and RIP2-deficient cells. RANKL-induced osteoclastogenesis was impaired in NOD2- and RIP2-deficient macrophages. We conclude that NOD2 is important for osteoclast differentiation and inflammatory bone resorption in vivo and also for the macrophage response to Gram-negative bacteria.National Institute of Dental and Craniofacial ResearchDepartment of Diagnosis and Surgery School of Dentistry at Araraquara Univ Estadual Paulista (UNESP), Rua Humaita, 1680, CentroDepartment of Microbiology Institute of Biomedical Sciences-Univ de Sao Paulo (USP)Department of Physiology and Pathology School of Dentistry at Araraquara-Univ Estadual Paulista (UNESP)Department of Cell Molecular Biology and Biopathogenic Agents School of Medicine at Ribeirao Preto-Univ de Sao Paulo (USP)Department of Periodontics School of Dental Medicine-University of PennsylvaniaDepartment of Diagnosis and Surgery School of Dentistry at Araraquara Univ Estadual Paulista (UNESP), Rua Humaita, 1680, CentroDepartment of Physiology and Pathology School of Dentistry at Araraquara-Univ Estadual Paulista (UNESP)National Institute of Dental and Craniofacial Research: R01DE017732National Institute of Dental and Craniofacial Research: R01DE021921Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)School of Dental Medicine-University of PennsylvaniaSouza, Joao A.C. [UNESP]Medeiros, Marcell C. [UNESP]Rocha, Fernanda R.G. [UNESP]De Aquino, Sabrina G. [UNESP]Ávila-Campos, Mario J.Spolidorio, Luis C. [UNESP]Zamboni, Dario S.Graves, Dana T.Rossa, Carlos [UNESP]2018-12-11T17:07:05Z2018-12-11T17:07:05Z2016-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article598-611application/pdfhttp://dx.doi.org/10.1177/1753425916666652Innate Immunity, v. 22, n. 8, p. 598-611, 2016.1753-42671753-4259http://hdl.handle.net/11449/17365110.1177/17534259166666522-s2.0-849920466172-s2.0-84992046617.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInnate Immunity1,0311,031info:eu-repo/semantics/openAccess2023-11-20T06:15:41Zoai:repositorio.unesp.br:11449/173651Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:15:54.790748Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
title Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
spellingShingle Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
Souza, Joao A.C. [UNESP]
Bone resorption
inflammation
innate immunity
macrophages
NOD2 signaling adaptor protein
title_short Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
title_full Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
title_fullStr Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
title_full_unstemmed Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
title_sort Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
author Souza, Joao A.C. [UNESP]
author_facet Souza, Joao A.C. [UNESP]
Medeiros, Marcell C. [UNESP]
Rocha, Fernanda R.G. [UNESP]
De Aquino, Sabrina G. [UNESP]
Ávila-Campos, Mario J.
Spolidorio, Luis C. [UNESP]
Zamboni, Dario S.
Graves, Dana T.
Rossa, Carlos [UNESP]
author_role author
author2 Medeiros, Marcell C. [UNESP]
Rocha, Fernanda R.G. [UNESP]
De Aquino, Sabrina G. [UNESP]
Ávila-Campos, Mario J.
Spolidorio, Luis C. [UNESP]
Zamboni, Dario S.
Graves, Dana T.
Rossa, Carlos [UNESP]
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade de São Paulo (USP)
School of Dental Medicine-University of Pennsylvania
dc.contributor.author.fl_str_mv Souza, Joao A.C. [UNESP]
Medeiros, Marcell C. [UNESP]
Rocha, Fernanda R.G. [UNESP]
De Aquino, Sabrina G. [UNESP]
Ávila-Campos, Mario J.
Spolidorio, Luis C. [UNESP]
Zamboni, Dario S.
Graves, Dana T.
Rossa, Carlos [UNESP]
dc.subject.por.fl_str_mv Bone resorption
inflammation
innate immunity
macrophages
NOD2 signaling adaptor protein
topic Bone resorption
inflammation
innate immunity
macrophages
NOD2 signaling adaptor protein
description NOD2 is a member of the NLR family of proteins that participate in the activation of the innate immune response. RIP2 is a downstream kinase activated by both NOD1 and NOD2. There is scarcity of information regarding the relevance of NOD2 in periodontitis, a chronic inflammatory condition characterized by inflammatory bone resorption. We used NOD2-KO and RIP2-KO mice in a model of microbial-induced periodontitis. Heat-killed Aggregatibacter actinomycetemcomitans was injected in the gingival tissues three times/wk for 4 wk. Bone resorption was assessed by μCT analysis; osteoclasts were identified by immunohistochemical staining for TRAP and inflammation was assessed using a severity score system in H/E-stained sections. In vitro studies using primary macrophages assessed the response macrophages using qPCR-based array and multi-ligand ELISA. Bone resorption and osteoclastogenesis were significantly reduced in NOD2-KO mice. Severity of inflammation was not affected. qPCR-focused arrays and multi-ligand ELISA showed that expression of pro-inflammatory mediators was reduced in NOD2- and RIP2-deficient cells. RANKL-induced osteoclastogenesis was impaired in NOD2- and RIP2-deficient macrophages. We conclude that NOD2 is important for osteoclast differentiation and inflammatory bone resorption in vivo and also for the macrophage response to Gram-negative bacteria.
publishDate 2016
dc.date.none.fl_str_mv 2016-11-01
2018-12-11T17:07:05Z
2018-12-11T17:07:05Z
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.uri.fl_str_mv http://dx.doi.org/10.1177/1753425916666652
Innate Immunity, v. 22, n. 8, p. 598-611, 2016.
1753-4267
1753-4259
http://hdl.handle.net/11449/173651
10.1177/1753425916666652
2-s2.0-84992046617
2-s2.0-84992046617.pdf
url http://dx.doi.org/10.1177/1753425916666652
http://hdl.handle.net/11449/173651
identifier_str_mv Innate Immunity, v. 22, n. 8, p. 598-611, 2016.
1753-4267
1753-4259
10.1177/1753425916666652
2-s2.0-84992046617
2-s2.0-84992046617.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Innate Immunity
1,031
1,031
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 598-611
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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