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Yuki Hosokawa, Kouji Hirao, Hiromichi Yumoto, Ayako Washio, Tadashi Nakanishi, Daisuke Takegawa, Chiaki Kitamura, Takashi Matsuo
Caries-related pathogens are first recognized by odontoblasts and induce inflammatory events that develop to pulpitis. Generally, initial sensing of microbial pathogens is mediated by pattern recognition receptors, such as Toll-like receptor and nucleotide-binding oligomerization domain (NOD); however, little is known about NODs in odontoblasts. In this study, the levels of NODs expressed in rat odontoblastic cell line, KN-3, were assessed by flow cytometry and the levels of chemokines in NOD-specific ligand-stimulated KN-3 cells were analyzed by real-time PCR and ELISA...
2016: BioMed Research International
Sukhithasri Vijayrajratnam, Anju Choorakottayil Pushkaran, Aathira Balakrishnan, Anilkumar Vasudevan, Raja Gopi Biswas, Chethampadi Gopi Mohan
Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is an intracellular pattern recognition receptor that recognizes bacterial peptidoglycan (PG) containing meso -diaminopimelic acid ( meso DAP) and activates the innate immune system. Interestingly, few pathogenic and commensal bacteria modify their PG stem peptide by amidation of meso DAP ( meso DAPNH2). In this study, NOD1 stimulation assays were performed using bacterial PG containing meso DAP (PGDAP) and meso DAPNH2 (PGDAPNH2) to understand the differences in their biomolecular recognition mechanism...
October 14, 2016: Biochemical Journal
Thomas A Kufer, Giulia Nigro, Philippe J Sansonetti
NOD-like receptor (NLR) proteins, as much as Toll-like receptor proteins, play a major role in modulating myeloid cells in their immune functions. There is still, however, limited knowledge on the expression and function of several of the mammalian NLR proteins in myeloid lineages. Still, the function of pyrin domain-containing NLR proteins and NLRC4/NAIP as inflammasome components that drive interleukin-1β (IL-1β) and IL-18 maturation and secretion upon pathogen stimulation is well established. NOD1, NOD2, NLRP3, and NLRC4/NAIP act as bona fide pattern recognition receptors (PRRs) that sense microbe-associated molecular patterns (MAMPs) but also react to endogenous danger-associated molecular patterns (DAMPs)...
August 2016: Microbiology Spectrum
Claire L Feerick, Declan P McKernan
NOD-like receptors (NLRs) are a family of 23 receptors known as pattern recognition receptors (PRRs), they are expressed in many cell types and play a key role in the innate immune response. The NLRs are activated by pathogen associated molecular patterns (PAMPs) which include structurally conserved molecules present on the surfaces of bacteria. The activation of these NLRs by pathogens results in the downstream activation of signalling kinases and transcription factors, culminating in the transcription of genes coding for pro-inflammatory factors...
October 5, 2016: Immunology
Qinghua Yang, Jianyi Liao, Jie Huang, Yi Ping Li, Shungen Huang, Huiting Zhou, Yi Xie, Jian Pan, Yanhong Li, Jiang Huai Wang, Jian Wang
In the present study, we aimed to examine the impact of cardiopulmonary bypass (CPB) on expression and function of NOD1 and NOD2 in children with congenital heart disease (CHD), in an attempt to clarify whether NOD1 and NOD2 signaling is involved in the modulation of host innate immunity against postoperative infection in pediatric CHD patients. Peripheral blood samples were collected from pediatric CHD patients at five different time points: before CPB, immediately after CPB, and 1, 3, and 7 days after CPB...
2016: PloS One
Vivekanandhan Aravindhan, Haridoss Madhumitha
Globally, noncommunicable chronic diseases such as Type-2 Diabetes Mellitus (T2DM) and Coronary Artery Disease (CAD) are posing a major threat to the world. T2DM is known to potentiate CAD which had led to the coining of a new clinical entity named diabetic CAD (DM-CAD), leading to excessive morbidity and mortality. The synergistic interaction between these two comorbidities is through sterile inflammation which is now being addressed as metabolic inflammation or metainflammation, which plays a pivotal role during both early and late stages of T2DM and also serves as a link between T2DM and CAD...
2016: Journal of Diabetes Research
Joao Ac Souza, Marcell C Medeiros, Fernanda Rg Rocha, Sabrina G de Aquino, Mario J Ávila-Campos, Luis C Spolidorio, Dario S Zamboni, Dana T Graves, Carlos Rossa
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...
September 7, 2016: Innate Immunity
Kaja Keček Plešec, Dunja Urbančič, Martina Gobec, Aleksandra Pekošak, Tihomir Tomašič, Marko Anderluh, Irena Mlinarič-Raščan, Žiga Jakopin
NOD1 and NOD2 are important members of the pattern recognition receptor family and play a crucial role within the context of innate immunity. However, overactivation of NODs, especially of NOD1, has also been implicated in a number of diseases. Surprisingly, NOD1 remains a virtually unexploited target in this respect. To gain additional insight into the structure-activity relationships of NOD1 inhibitors, a series of novel analogs has been designed and synthesized and then screened for their NOD1-inhibitory activity...
November 1, 2016: Bioorganic & Medicinal Chemistry
Tae-Joon Hong, Ji-Sook Hahn
NOD1 is an intracellular sensor of innate immunity which is related to a number of inflammatory diseases. NOD1 is known to be difficult to express and purify for structural and biochemical studies. Based on the fact that Hsp90 and its cochaperone SGT1 are necessary for the stabilization and activation of NOD1 in mammals, SGT1 was chosen as a fusion partner of the leucine-rich repeat (LRR) domain of NOD1 for its soluble expression in Escherichia coli. Fusion of human SGT1 (hSGT1) to NOD1 LRR significantly enhanced the solubility, and the fusion protein was stabilized by coexpression of mouse Hsp90α...
September 30, 2016: Biochemical and Biophysical Research Communications
Leong-Perng Chan, Ling-Feng Wang, Feng-Yu Chiang, Ka-Wo Lee, Po-Lin Kuo, Chia-Hua Liang
NOD1 (nucleotide-binding oligomerization domain 1) is overexpressed in head and neck squamous cell carcinoma (HNSCC) cells, as is IL-8 in cancer cells. However, the mechanism of the IL-8-mediated overexpression of NOD in HNSCC not been identified. This study determines whether IL-8 promotes tumor progression via the NOD signaling pathway in HNSCC. Higher IL-8, NOD1 and receptor-interacting protein kinase (RIP2) expressions were observed in HNSCC tissue than in non-cancerous matched tissue (NCMT), whereas NOD2 was weakly expressed...
August 20, 2016: Oncotarget
Shaokui Chen, Yulan Liu, Xiuying Wang, Haibo Wang, Shuang Li, Haifeng Shi, Huiling Zhu, Jing Zhang, Dingan Pi, Chien-An Andy Hu, Xi Lin, Jack Odle
Asparagine (Asn), an activator of ornithine decarboxylase (ODC), stimulates cell proliferation in intestinal epithelial cells. We hypothesized that Asn can mitigate LPS-induced injury of intestinal structure and barrier function by regulating inflammatory signaling pathways. We executed the following experiment using weanling pigs for each of the groups: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 0.5% Asn; (4) LPS + 1.0% Asn. After 21-d feeding, pigs received an i.p. injection of either saline or LPS...
August 22, 2016: Innate Immunity
Yulia A Dagil, Nikolai P Arbatsky, Biana I Alkhazova, Vyacheslav L L'vov, Dmitriy V Mazurov, Mikhail V Pashenkov
Muropeptides are fragments of peptidoglycan that trigger innate immune responses by activating nucleotide-binding oligomerization domain (NOD) 1 and NOD2. Muropeptides from Gram-negative bacteria contain a meso-diaminopimelic acid (meso-DAP) residue in either a terminal or a non-terminal position. While the former ones are known to be recognized by NOD1, much less is known about recognition of muropeptides with non-terminal meso-DAP, which are most abundant moieties of Gram-negative peptidoglycans. Here, we developed a novel system to assess biological activity of muropeptides, based on CRISPR/Cas9-mediated knockout (KO) of NOD1 and NOD2 genes in modified HEK293T cells...
2016: PloS One
Julia Metzger, Sophia Pfahler, Ottmar Distl
BACKGROUND: The Lundehund is a highly specialized breed characterized by a unique flexibility of the joints and polydactyly in all four limbs. The extremely small population size and high inbreeding has promoted a high frequency of diseased dogs affected by the Lundehund syndrome (LS), a severe gastro-enteropathic disease. RESULTS: Comprehensive analysis of bead chip and whole-genome sequencing data for LS in the Lundehund resulted in a genome-wide association signal on CFA 34 and LS-specific runs of homozygosity (ROH) in this region...
2016: BMC Genomics
João Antônio Chaves de Souza, Sabrina Cruz Tfaile Frasnelli, Fabiana de Almeida Curylofo, Mário Julio Ávila Campos, Luis Carlos Spolidório, Dario Simões Zamboni, Dana T Graves, Carlos Rossa Junior
Periodontitis is a chronic inflammatory condition characterized by destruction of non-mineralized and mineralized connective tissues. It is initiated and maintained by a dysbiosis of the bacterial biofilm adjacent to teeth with increased prevalence of Gram-negative microorganisms. NOD1 is a member of the Nod-like receptors (NLRs) family of proteins that participate in the activation of the innate immune system, in response to invading bacteria or to bacterial antigens present in the cytoplasm. The specific activating ligand for NOD1 is a bacterial peptidoglycan derived primarily from Gram-negative bacteria...
August 1, 2016: Immunology
Yan Zou, Wenbo Lei, Zhansheng He, Zhongyu Li
Chlamydial species are common intracellular parasites that cause various diseases, mainly characterized by persistent infection, which lead to inflammatory responses modulated by pattern recognition receptors (PRRs). The best understood PRRs are the extracellular Toll-like receptors, but recent significant advances have focused on two important proteins, NOD1 and NOD2, which are members of the intracellular nucleotide-binding oligomerization domain receptor family and are capable of triggering the host innate immune signaling pathways...
September 2016: FEMS Microbiology Letters
Youssef Darzi, Yizu Jiao, Mizuho Hasegawa, Henry Moon, Gabriel Núñez, Naohiro Inohara, Jeroen Raes
Strain NI1060 is an oral bacterium responsible for periodontitis in a murine ligature-induced disease model. To better understand its pathogenicity, we have determined the complete sequence of its 2,553,982 bp genome. Although closely related to Pasteurella pneumotropica, a pneumonia-associated rodent commensal based on its 16S rRNA, the NI1060 genomic content suggests that they are different species thriving on different energy sources via alternative metabolic pathways. Genomic and phylogenetic analyses showed that strain NI1060 is distinct from the genera currently described in the family Pasteurellaceae, and is likely to represent a novel species...
2016: PloS One
Jasmin Schnerch, Antje Prasse, Dimitrios Vlachakis, Katrin L Schuchardt, Dmitri V Pechkovsky, Torsten Goldmann, Karoline I Gaede, Joachim Müller-Quernheim, Gernot Zissel
BACKGROUND: Sarcoidosis is a granulomatous disease characterized by a Th1-cell dominated alveolitis. As a role of bacteria in the pathogenesis of sarcoidosis has been discussed, toll-like receptors (TLR) may be involved in the initiation of a first immune reaction. OBJECTIVES: We analysed expression and functional relevance of several TLRs in broncho-alveolar lavage (BAL) cells from patients with pulmonary sarcoidosis. In parallel, we determined the release of CXCL9, CXCL10, and CXCL11 by BAL cells from patients with pulmonary sarcoidosis...
July 8, 2016: American Journal of Respiratory Cell and Molecular Biology
Liang-Jun Wei, Xun Tan, Guo-Juan Fan, Ya-Nan Jiang, Qurban A Shah
Cytosolic nucleotide oligomerisation domain (NOD)-like receptors play an important role in host defence against infection. Reduced NOD1 expression has been observed in dysfunctional neutrophils derived from periparturient cattle known to be most susceptible to coliform mastitis. However, whether impairment of NOD1 suppresses the immune responses of bovine neutrophils during bacterial infections remains unknown. Crude (phenol extracted) lipopolysaccharide (cLPS), which often contains other immunostimulatory molecules, including NOD1 agonist, is known to induce almost the whole bacterial response...
August 2016: Veterinary Journal
Mariana X Byndloss, Arina Marijke Keestra-Gounder, Andreas J Bäumler, Renée M Tsolis
Although viruses have long been known to subvert the endoplasmic reticulum (ER) for their replication, recent work has shown that this strategy is also used by bacterial pathogens and parasites to promote their intracellular growth. The ensuing disruption of cellular processes triggers a condition known as ER stress, which activates the host cell's unfolded protein response (UPR) to restore homeostasis. Recent work has linked the UPR, in particular the arm of this response that depends on the ER-resident sensor IRE1, to innate immunity and inflammation...
July 2016: DNA and Cell Biology
Roberta Caruso, Gabriel Núñez
NOD1 and NOD2, two members of the intracellular NOD-like receptor family, sense bacterial peptidoglycan-derived fragments and induce pro-inflammatory responses. Recent work provides evidence for a role for NOD1/NOD2 signaling in mediating ER-stress-induced inflammatory responses via a peptidoglycan-independent mechanism.
June 20, 2016: Current Biology: CB
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