Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss. 2013

Huaiping Yuan, and Sami Zelkha, and Sami Zelka, and Marina Burkatovskaya, and Rohit Gupte, and Susan E Leeman, and Salomon Amar
Center for Anti-Inflammatory Therapeutics, School of Dental Medicine and Department of Pharmacology, School of Medicine, Boston University, Boston, MA 02118.

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.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D000119 Acetylmuramyl-Alanyl-Isoglutamine Peptidoglycan immunoadjuvant originally isolated from bacterial cell wall fragments; also acts as pyrogen and may cause arthritis; stimulates both humoral and cellular immunity. Mur-NAc-L-Ala-D-isoGln,Muramyl Dipeptide,Acetylmuramyl Alanyl Isoglutamine,N-Acetyl-Muramyl-L-Alanyl-D-Glutamic-alpha-Amide,N-Acetylmuramyl-L-Alanyl-D-Isoglutamine,Alanyl Isoglutamine, Acetylmuramyl,Dipeptide, Muramyl,Isoglutamine, Acetylmuramyl Alanyl,Mur NAc L Ala D isoGln,N Acetyl Muramyl L Alanyl D Glutamic alpha Amide,N Acetylmuramyl L Alanyl D Isoglutamine
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001057 Apolipoproteins E A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III. Apo-E,Apo E,Apo E Isoproteins,ApoE,Apolipoprotein E Isoproteins,Apoprotein (E),Apoproteins E,Isoproteins, Apo E,Isoproteins, Apolipoprotein E
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016301 Alveolar Bone Loss Resorption or wasting of the tooth-supporting bone (ALVEOLAR PROCESS) in the MAXILLA or MANDIBLE. Alveolar Resorption,Bone Loss, Alveolar,Bone Loss, Periodontal,Periodontal Bone Loss,Periodontal Resorption,Alveolar Bone Atrophy,Alveolar Process Atrophy,Alveolar Bone Atrophies,Alveolar Bone Losses,Alveolar Process Atrophies,Alveolar Resorptions,Bone Atrophies, Alveolar,Bone Atrophy, Alveolar,Bone Losses, Periodontal,Periodontal Bone Losses,Periodontal Resorptions,Resorption, Alveolar,Resorption, Periodontal,Resorptions, Alveolar
D016866 Bacteroidaceae Infections Infections with bacteria of the family BACTEROIDACEAE. Infections, Bacteroidaceae,Bacteroidaceae Infection,Infection, Bacteroidaceae
D016966 Porphyromonas gingivalis A species of gram-negative, anaerobic, rod-shaped bacteria originally classified within the BACTEROIDES genus. This bacterium produces a cell-bound, oxygen-sensitive collagenase and is isolated from the human mouth. Bacteroides gingivalis

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