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NOD like receptor

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https://www.readbyqxmd.com/read/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#1
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27912077/nlrp3-activation-induces-il-18-synthesis-and-affects-the-epithelial-barrier-function-in-reactive-cholangiocytes
#2
Luca Maroni, Laura Agostinelli, Stefania Saccomanno, Claudio Pinto, Debora Giordano, Chiara Rychlicki, Samuele De Minicis, Luciano Trozzi, Jesus M Banales, Espen Melum, Tom H Karlsen, Antonio Benedetti, Gianluca Svegliati Baroni, Marco Marzioni
Microbial products are thought to influence the progression of cholangiopathies, in particular primary sclerosing cholangitis (PSC). Inflammasomes are molecular platforms that respond to microbial products through the synthesis of proinflammatory cytokines. We investigated the role of inflammasome activation in cholangiocyte response to injury. Nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing protein 3 (Nlrp3) expression was tested in cholangiocytes of normal and cholestatic livers...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#3
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27893720/a-functional-atg16l1-t300a-variant-is-associated-with-necrotizing-enterocolitis-in-premature-infants
#4
Venkatesh Sampath, Vineet Bhandari, Jessica Berger, Daniel Merchant, Liyun Zhang, Mihoko Ladd, Heather Menden, Jeffery Garland, Namasivayam Ambalavanan, Neil Mulrooney, Michael Quasney, John Dagle, Pascal M Lavoie, Pippa Simpson, Mary Dahmer
BACKGROUND: The genetic basis of dysfunctional immune responses in necrotizing enterocolitis (NEC) remains unknown. We hypothesized that variants in Nucleotide binding and Oligomerization Domain (NOD)-Like Receptors (NLRs) and Autophagy (ATG) genes modulate vulnerability to NEC. METHODS: We genotyped a multi-center cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8 and NLRP3 variants. Chi-square tests and logistic regression were used for statistical analysis...
November 28, 2016: Pediatric Research
https://www.readbyqxmd.com/read/27889463/noncanonical-fungal-autophagy-inhibits-inflammation-in-response-to-ifn-%C3%AE-via-dapk1
#5
Vasilis Oikonomou, Silvia Moretti, Giorgia Renga, Claudia Galosi, Monica Borghi, Marilena Pariano, Matteo Puccetti, Carlo A Palmerini, Lucia Amico, Alessandra Carotti, Lucia Prezioso, Angelica Spolzino, Andrea Finocchi, Paolo Rossi, Andrea Velardi, Franco Aversa, Valerio Napolioni, Luigina Romani
Defects in a form of noncanonical autophagy, known as LC3-associated phagocytosis (LAP), lead to increased inflammatory pathology during fungal infection. Although LAP contributes to fungal degradation, the molecular mechanisms underlying LAP-mediated modulation of inflammation are unknown. We describe a mechanism by which inflammation is regulated during LAP through the death-associated protein kinase 1 (DAPK1). The ATF6/C/EBP-β/DAPK1 axis activated by IFN-γ not only mediates LAP to Aspergillus fumigatus but also concomitantly inhibits Nod-like receptor protein 3 (NLRP3) activation and restrains pathogenic inflammation...
November 16, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27885718/purinergic-receptors-new-targets-for-the-treatment-of-gout-and-fibrosis
#6
REVIEW
Thomas Gicquel, Brendan Le Daré, Elisabeth Boichot, Vincent Lagente
Adenosine triphosphate is involved in many metabolic reactions, but it has also a role as a cellular danger signal transmitted through purinergic receptors (PRs). Indeed, ATP can bind to PRs which are found in the membrane of many cell types, although the relative proportions of the receptor subtypes differ. PRs are classified according to genetic and pharmacological criteria and especially their affinities for agonists and their transduction mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP release by activated or necrotic cells may activate various PRs and especially P2X7R, the best-characterized PR, on immune cells...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27885704/effects-of-genetic-variations-in-the-genes-encoding-nod1-and-nod2-on-type-2-diabetes-mellitus-and-insulin-resistance
#7
C Ozbayer, H Kurt, M N Kebapci, H V Gunes, E Colak, I Degirmenci
WHAT IS KNOWN AND OBJECTIVE: Nucleotide-binding oligomerization domain (NOD) 1 and NOD 2 are members of the NOD-like receptor (NLR) family and contain a caspase recruitment domain. NLRs are located in the cytosol, bind bacterial and viral ligands and play a key role in the realization of innate and adaptive immune response, inflammation, apoptosis and reactive oxygen species generation. Insulin resistance (IR) is a leading cause of type 2 diabetes mellitus (T2DM) and associated with obesity, inflammation and pro-inflammatory responses...
November 25, 2016: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27880990/neurodegeneration-and-nlrp3-inflammasome-expression-in-the-anterior-thalamus-of-sod1-g93a-als-mice
#8
Berthold Debye, Lena Schmülling, Lepu Zhou, Gabriele Rune, Cordian Beyer, Sonja Johann
Nowadays, Amyotrophic lateral sclerosis (ALS) is considered as a multisystem disorder, characterized by a primary degeneration of motor neurons as well as neuropathological changes in non-motor regions. Neurodegeneration in subcortical areas, such as the thalamus, are believed to contribute to cognitive and behavioural abnormalities in ALS patients. In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS...
November 23, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27876605/role-of-zebrafish-nlrc5-in-antiviral-response-and-transcriptional-regulation-of-mhc-related-genes
#9
Xiao Man Wu, Yi Wei Hu, Na Na Xue, Shi Si Ren, Shan Nan Chen, Pin Nie, Ming Xian Chang
Intracellular NOD-like receptors (NLRs) are emerging as critical regulators of innate and adaptive immune responses. Although the NLR family member NLRC5 is functionally defined, the role of NLRC5 in regulating innate immune signaling has been controversial in mammals, and is poorly understood in teleost fish. In the present study, we report the functional characterization of zebrafish NLRC5. The cloned NLRC5 consists of 6435 bp which encodes 1746 amino acids. The N-terminal effector-binding domain of zebrafish NLRC5 is absent which is different from all other human NLRs...
November 20, 2016: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/27875342/the-multifaceted-roles-of-inflammasome-proteins-in-cancer
#10
Virginie Petrilli
PURPOSE OF REVIEW: Inflammasomes are major actors of the innate immune system, through their regulation of inflammatory caspases and maturation of IL-1β and IL-18. These multiprotein complexes have been shown to play major roles in inflammatory and metabolic diseases and have more recently been implicated in tumor development and dissemination. In this review, we address these recent findings, focusing particularly on colorectal cancer (CRC) initiation and tumor dissemination. RECENT FINDINGS: Based mostly on loss-of-function experiments in mouse models, paradoxical results were obtained as both protumoral and antitumoral activities were reported...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27872860/danggui-buxue-tang-attenuates-tubulointerstitial-fibrosis-via-suppressing-nlrp3-inflammasome-in-a-rat-model-of-unilateral-ureteral-obstruction
#11
Linna Wang, Jiwei Ma, Cunxia Guo, Changyong Chen, Zhong Yin, Xueguang Zhang, Xiangmei Chen
Inflammation significantly contributes to the progression of chronic kidney disease (CKD). This study aimed to characterize Danggui Buxue Tang (DBT) renoprotection and relationship with NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome expression in rats with unilateral ureteral obstruction (UUO). Sprague-Dawley rats were subjected to UUO and randomly assigned to untreated UUO, enalapril-treated (10 mg/kg/day), and DBT-treated (9 g/kg/day) groups. Sham-operated rats served as controls, with 8 rats in each group...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27864235/l5-ldl-from-st-elevation-myocardial-infarction-patients-induces-il-1%C3%AE-production-via-lox-1-and-nlrp3-inflammasome-activation-in-macrophages
#12
Tzu-Ching Yang, Po-Yuan Chang, Shao-Chun Lu
L5-LDL, the most electronegative LDL associated with major cardiovascular risks, significantly rises in patients with ST-segment elevation myocardial infarction (STEMI). The inflammatory nature of atherosclerotic vascular diseases has prompted us to investigate whether L5-LDL induces the production of inflammatory cytokines, especially vascular ischemia-related interleukin (IL)-1β in the pathogenesis of STEMI. Clinical data showed that plasma levels of L5-LDL and IL-1β were higher in the STEMI patients than in the controls (p < 0...
November 18, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27863839/antihyperuricemic-effect-of-liquiritigenin-in-potassium-oxonate-induced-hyperuricemic-rats
#13
Long Hongyan, Wu Suling, Zhu Weina, Zhang Yajie, Ruan Jie
The aim is to investigate the anti-hyperuricemic and renal protective effects of liquiritigenin in potassium oxonate-induced hyperuricemic rats. Hyperuricemia in rats was induced were induced with potassium oxonate (250mg/kg) intragastrically for 7 days, and liquiritigenin (20, 40mg/kg) and allopurinol (5mg/kg) were daily administrated to the rats orally 1h after the potassium oxonate exposure. Liquiritigenin significantly reversed the elevated productions of uric acid in serum and urine and pro-inflammation cytokines in serum and kidney, which shown that liquiritigenin has renal protective effects...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27856455/map3k8-modulates-monocyte-state-and-atherogenesis-in-apoe-mice
#14
Carlos Sanz-Garcia, Ángela Sánchez, Constanza Contreras-Jurado, Carmela Cales, Cristina Barranquero, Marta Muñóz, Ramón Merino, Paula Escudero, Maria-Jesús Sanz, Jesús Osada, Ana Aranda, Susana Alemany
OBJECTIVE: Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-αR, NOD-2R, adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. APPROACH AND RESULTS: We show here that Map3k8 deficiency results in smaller numbers of Ly6C(high)CD11c(low) and Ly6C(low)CD11c(high) monocytes in ApoE(-)(/-) mice fed a high-fat diet (HFD)...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27843150/the-bacterial-peptidoglycan-sensing-molecule-pglyrp2-modulates-brain-development-and-behavior
#15
T Arentsen, Y Qian, S Gkotzis, T Femenia, T Wang, K Udekwu, H Forssberg, R Diaz Heijtz
Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27825391/oestrous-cycle-dependent-equine-uterine-immune-response-to-induced-infectious-endometritis
#16
Christina D Marth, Simon M Firestone, Lisa Y Glenton, Glenn F Browning, Neil D Young, Natali Krekeler
Infectious endometritis is a major cause of reduced pregnancy rates in horses. The objectives of this study were to establish a timeline of the innate immune response in the uterus of healthy horses and to investigate the oestrous cycle effect on this. Endometrial biopsies were collected from five horses before and at 3, 12, 24, 48 and 72 h after inoculation of Escherichia coli, once in oestrus and once in dioestrus. They were analysed by quantitative real-time PCR, microbiology and histology. Neutrophil numbers increased from very low levels in the absence of inflammation to severe neutrophilia 3 h after inoculation...
November 8, 2016: Veterinary Research
https://www.readbyqxmd.com/read/27820602/an-interferon-%C3%AE-resistant-and-nlrp3-inflammasome-independent-subtype-of-eae-with-neuronal-damage
#17
Makoto Inoue, Po-Han Chen, Stephen Siecinski, Qi-Jing Li, Chunlei Liu, Lawrence Steinman, Simon G Gregory, Eric Benner, Mari L Shinohara
Inflammation induced by innate immunity influences the development of T cell-mediated autoimmunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We found that strong activation of innate immunity induced Nod-like receptor protein 3 (NLRP3) inflammasome-independent and interferon-β (IFNβ)-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFNβ treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-β receptor (LTβR) and CXC chemokine receptor 2 (CXCR2), is involved in type B EAE development, and type B EAE is ameliorated by antagonizing these receptors...
November 7, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27819323/donor-and-recipient-genetic-variants-in-nlrp3-associate-with-early-acute-rejection-following-kidney-transplantation
#18
Mark C Dessing, Jesper Kers, Jeffrey Damman, Gerjan J Navis, Sandrine Florquin, Jaklien C Leemans
NLRP3 (NOD-like receptor family, pyrin domain containing 3) is a member of the inflammasome family and is of special interest in renal disease. Experimental studies have shown that Nlrp3 plays a significant role in the induction of renal damage and dysfunction in acute and chronic renal injury. However, the role of NLRP3 in human renal disease is completely unknown. From a retrospective cohort study, we determined in 1271 matching donor and recipient samples if several NLRP3 single nucelotide polymorphisms (SNPs) were associated with primary non-function (PNF), delayed graft function (DGF), biopsy-proven acute rejection (BPAR) and death-censored graft and patient survival...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815826/rig-i-like-receptor-induced-irf3-mediated-pathway-of-apoptosis-ripa-a-new-antiviral-pathway
#19
REVIEW
Saurabh Chattopadhyay, Ganes C Sen
The innate immune response is the first line of host defense to eliminate viral infection. Pattern recognition receptors in the cytosol, such as RIG-I-like receptors (RLR) and Nod-like receptors (NLR), and membrane bound Toll like receptors (TLR) detect viral infection and initiate transcription of a cohort of antiviral genes, including interferon (IFN) and interferon stimulated genes (ISGs), which ultimately block viral replication. Another mechanism to reduce viral spread is through RIPA, the RLR-induced IRF3-mediated pathway of apoptosis, which causes infected cells to undergo premature death...
November 4, 2016: Protein & Cell
https://www.readbyqxmd.com/read/27812365/shared-genetic-etiology-of-autoimmune-diseases-in-patients-from-a-biorepository-linked-to-de-identified-electronic-health-records
#20
Nicole A Restrepo, Mariusz Butkiewicz, Josephine A McGrath, Dana C Crawford
: Autoimmune diseases represent a significant medical burden affecting up to 5-8% of the U.S. POPULATION: While genetics is known to play a role, studies of common autoimmune diseases are complicated by phenotype heterogeneity, limited sample sizes, and a single disease approach. Here we performed a targeted genetic association study for cases of multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease (CD) to assess which common genetic variants contribute individually and pleiotropically to disease risk...
2016: Frontiers in Genetics
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