Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , |
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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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 |
|
_version_ |
1808128913436573696 |