Role of NOD2 and RIP2 in host-microbe interactions with Gram-negative bacteria: Insights from the periodontal disease model
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2016-11-01
Autores
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]
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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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Bone resorption, inflammation, innate immunity, macrophages, NOD2 signaling adaptor protein
Como citar
Innate Immunity, v. 22, n. 8, p. 598-611, 2016.