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Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss
- Yuan, Huaiping, Zelka, Sami, Burkatovskaya, Marina, Gupte, Rohit, Leeman, Susan E., Amar, Salomon
- Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.52 pp. E5059
- Porphyromonas gingivalis, Toll-like receptor 2, animal models, anti-inflammatory activity, aorta, apolipoprotein E, atherosclerosis, blood serum, body weight changes, bone resorption, cholesterol, genes, heart, high fat diet, inflammation, intracellular signaling peptides and proteins, macrophages, messenger RNA, mice, mitogen-activated protein kinase, oligomerization, transcription factor NF-kappa B, tumor necrosis factor-alpha, weight gain
- The purpose of this study was to elucidate the role of nucleotide binding oligomerization domain-containing protein 2 (NOD2) signaling in atherosclerosis and periodontal bone loss using an Apolipoprotein E ⁻/⁻ (ApoE ⁻/⁻) mouse model based on the proposed role of NOD2 in inflammation. NOD2 ⁻/⁻ApoE ⁻/⁻ and ApoE ⁻/⁻ mice fed a standard chow diet were given an oral gavage of Porphyromonas gingivalis for 15 wk. NOD2 ⁻/⁻ApoE ⁻/⁻ mice exhibited significant increases in inflammatory cytokines, alveolar bone loss, cholesterol, and atherosclerotic lesions in the aorta and the heart compared with ApoE ⁻/⁻ mice. In contrast, ApoE ⁻/⁻ mice injected i.p. with Muramyl DiPeptide (MDP) to stimulate NOD2 and given an oral gavage of P. gingivalis displayed a reduction of serum inflammatory cytokines, alveolar bone loss, cholesterol, and atherosclerotic lesions in the aorta and aortic sinus compared with ApoE ⁻/⁻ mice orally challenged but injected with saline. A reduction in body weight gain was observed in ApoE ⁻/⁻ mice fed a high-fat diet (HFD) and injected with MDP compared with ApoE ⁻/⁻ mice fed a high-fat diet but injected with saline. MDP treatment of bone marrow-derived macrophages incubated with P. gingivalis increased mRNA expressions of NOD2, Toll-like receptor 2, myeloid differentiation primary response gene 88, and receptor-interacting protein-2 but reduced the expressions of inhibitor of NF-κB kinase-β, NF-κB, c-Jun N-terminal kinase 3, and TNF-α protein levels compared with saline control, highlighting pathways involved in MDP antiinflammatory effects. MDP activation of NOD2 should be considered in the treatment of inflammatory processes affecting atherosclerosis, periodontal bone loss ,and possibly, diet-induced weight gain.