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Cansu Ozbayer, Hulyam Kurt, Aysegul Bayramoglu, Hasan Veysi Gunes, Muzaffer Metintas, İrfan Degirmenci, Kevser Setenay Oner
BACKGROUND AND AIM: NOD1/CARD4 and NOD2/CARD15 are members of the Nod-like receptor (NLR) family, and they contain a caspase recruitment domain (CARD). NLRs are located in the cytosol where they bind bacterial and viral ligands and play a key role in the innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. NLR gene polymorphisms may shift the balance between pro- and anti-inflammatory cytokines and modulate the risk of infection, chronic inflammation, and cancer...
October 2015: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Iwona Wybranska, Anna Polus, Magdalena Mikolajczyk, Anna Knapp, Agnieszka Sliwa, Barbara Zapala, Teresa Staszel, Aldona Dembinska-Kiec
The expression of apoptosis genes in a commercial pre-designed low-density array from Applied Biosystems was evaluated in two human brain cancer cell models, LN-18 and Daoy (HTB-186™) in comparison to the reference human primary endothelial cells under basic conditions. Analysis of the gene expression in the cancer cell lines compared to the normal control revealed features reflecting anti-apoptotic and inflammatory characteristics of the former. There was an overall downregulation of apoptosis-stimulating genes in both cancer cell lines, along with an upregulation of certain apoptosis inhibitors...
December 2013: Human Cell
Monika Sharma
Apoptosis-antagonizing transcription factor (AATF) is involved in transcriptional regulation, cell cycle control, DNA damage responses and in the execution of cell death programs. It also interacts directly with nuclear hormone receptors to enhance their transactivation. This study highlights the RNomics of AATF gene in the pathogenesis of breast cancer: RNA interference gave 64% reduction in AATF mRNA and 47% decline in AATF protein expression in MCF-7 breast cancer cells. Cell proliferation decreased by 41% after transfection and was accompanied by apoptosis induction in 30% MCF-7 cells...
October 2013: Biotechnology Letters
Adaikalavan Ramasamy, Ivan Curjuric, Lachlan J Coin, Ashish Kumar, Wendy L McArdle, Medea Imboden, Benedicte Leynaert, Manolis Kogevinas, Peter Schmid-Grendelmeier, Juha Pekkanen, Matthias Wjst, Andreas J Bircher, Ulla Sovio, Thierry Rochat, Anna-Liisa Hartikainen, David J Balding, Marjo-Riitta Jarvelin, Nicole Probst-Hensch, David P Strachan, Deborah L Jarvis
BACKGROUND: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. OBJECTIVE: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings...
November 2011: Journal of Allergy and Clinical Immunology
Anton G Kutikhin
NOD1/CARD4 and NOD2/CARD15 are members of Nod-like receptor family. They are located in cytosol, bind bacterial and viral ligands and play a key role in realization of innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. Polymorphisms in NOD1/CARD4 and NOD2/CARD15 genes may shift balance between pro- and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation and cancer. NOD1/CARD4 and NOD2/CARD15 gene polymorphisms may be associated with altered risk of gastric, colorectal, breast, ovarian, prostate, testicular, lung, laryngeal, liver, gallbladder, biliary tract, pancreatic, small bowel, kidney, urinary bladder cancer, skin cancer, nonthyroid endocrine tumors, lymphoma and leukemia...
October 2011: Human Immunology
Ravi Verma, Vineet Ahuja, Jaishree Paul
BACKGROUND AND AIM: The nucleotide-binding oligomerization domain-1 (NOD1) gene encodes a pattern recognition receptor that senses pathogens. NOD1/caspase recruitment domain (CARD4) signaling leads to the activation of nuclear factor-kB, and plays an important role in innate immunity. Certain polymorphisms and mutations in NOD1/CARD4 might result in a dysfunctional innate immune response during bacterial recognition, which might have direct implications in inflammatory bowel disease (IBD) pathogenesis...
January 2012: Journal of Gastroenterology and Hepatology
Wei-Guo Lu, Yan-Feng Zou, Xiao-Liang Feng, Feng-Lai Yuan, Yuan-Long Gu, Xia Li, Cheng-Wan Li, Cheng Jin, Jian-Ping Li
AIM: To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism is associated with inflammatory bowel disease by meta-analysis. METHODS: We surveyed the studies on the association of NOD1/CARD4 insertion/deletion polymorphism with inflammatory bowel disease in PubMed. Meta-analysis was performed for genotypes GG/T vs T/T, GG/GG vs T/T, GG/T + GG/GG vs T/T, GG/GG vs T/T + GG/T, and GG allele vs T allele in a fixed/random effect model. RESULTS: We identified 8 studies (6439 cases and 4798 controls) in Caucasian populations using PubMed search...
September 14, 2010: World Journal of Gastroenterology: WJG
Guanjun Cheng, Jing Sun, Zvi G Fridlender, Liang-Chuan S Wang, Lai-Ming Ching, Steven M Albelda
The cytosolic nucleotide-binding oligomerization domain 1 (NOD1)/CARD4 and NOD2/CARD15 proteins are members of NOD-like receptors recognizing specific motifs within peptidoglycans of both Gram-negative and Gram-positive bacteria. NOD1 and NOD2 signal via the downstream adaptor serine/threonine kinase RIP2/CARDIAK/RICK to initiate NF-kappaB activation and the release of inflammatory cytokines/chemokines. In this report, we show that 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a cell-permeable, small molecule that has anti-tumor activity, can also activate NOD1 and NOD2...
April 2, 2010: Journal of Biological Chemistry
Nikolaus Möckelmann, Witigo von Schönfels, Stephan Buch, Oliver von Kampen, Bence Sipos, Jan Hendrik Egberts, Philip Rosenstiel, Andre Franke, Mario Brosch, Sebastian Hinz, Christian Röder, Holger Kalthoff, Ulrich R Fölsch, Michael Krawczak, Stefan Schreiber, Clemens Dieter Bröring, Jürgen Tepel, Clemens Schafmayer, Jochen Hampe
BACKGROUND: Variation in genes involved in the innate immune response may play a role in the predisposition to colorectal cancer (CRC). Several polymorphisms of the CARD15 gene (caspase activating recruitment domain, member 15) have been reported to be associated with an increased susceptibility to Crohn disease. Since the CARD15 gene product and other CARD proteins function in innate immunity, we investigated the impact of germline variation at the CARD4, CARD8 and CARD15 loci on the risk for sporadic CRC, using a large patient sample from Northern Germany...
2009: BMC Gastroenterology
Simone Reuter, Jessica Charlet, Tom Juncker, Marie-Hélène Teiten, Mario Dicato, Marc Diederich
Curcumin, a natural product isolated from the plant Curcuma longa, has a diverse range of molecular targets that influence numerous biochemical and molecular cascades. Curcumin has been shown to inhibit nuclear factor kappaB (NF-kappaB) activation at several steps in the NF-kappaB signaling pathways and thereby controls numerous NF-kappaB-regulated genes involved in various diseases. In the present study, we investigated the effect of curcumin pretreatment on 84 tumor necrosis factor-alpha (TNF-alpha)-activated genes of NF-kappaB pathways in K562 cells, using a real-time PCR array...
August 2009: Annals of the New York Academy of Sciences
Bogdan Jakiela, Wojciech Szczeklik, Barbara Sokolowska, Lucyna Mastalerz, Marek Sanak, Hanna Plutecka, Andrzej Szczeklik
OBJECTIVES: Churg-Strauss syndrome (CSS) is a rare necrotizing vasculitis associated with asthma, blood and tissue eosinophilia and granuloma formation. We wondered whether eosinophil accumulation in CSS results from the defect of intrinsic apoptosis pathway in blood eosinophils, leading to their prolonged survival. METHODS: We analysed immunophenotype (flow cytometry), expression of apoptosis-related genes (real-time PCR) and spontaneous apoptosis in blood eosinophils isolated from nine patients in exacerbation (active CSS), seven patients in remission (inactive CSS) and 14 matched healthy subjects...
October 2009: Rheumatology
Man Xu, Ming-Shen Dai, Can Mi
AIM: To investigate the relationship between the activation of pattern recognition receptors and the cytokines expression of dendritic cells. METHODS: After bone marrow-derived dendritic cells (BMDCs) were pulsed by E.coli LLO/OVA, the mRNA expression of pattern recognition receptors and the downstream NF-kappaB signal pathway associated molecules were detected by microarray hybridization and RT-PCR; the expression of costimulatory molecules, MHC class II and cytokines were determined by flow cytometry and ELISA...
January 2009: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Xuhang Li, Laurie Conklin, Philip Alex
Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Sigma) two major oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (SigmaMan3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4)...
September 7, 2008: World Journal of Gastroenterology: WJG
Liesbet Henckaerts, Carolina Figueroa, Séverine Vermeire, Miquel Sans
The volume of research undertaken on the genetic susceptibility of inflammatory bowel disease (IBD) has been tremendous. Genome-wide linkage studies pointed towards more than 10 chromosomal regions and fine-mapping of these regions led to the identification of a number of genes, including CARD15 (NOD2), DLG5, OCTN1 and 2, TLR4 and CARD4 (NOD1). With the recent completion of the human genome project, whole genome association studies (WGAS) have now become possible and have identified additional genes (IL23R, IRGM, PTGER4, ATG16L1) for Crohn's disease and ulcerative colitis, that have subsequently been replicated...
May 2008: Current Drug Targets
P L Lakatos, I Altorjay, Y Mándi, L Lakatos, J Tumpek, A Kovacs, T Molnar, Z Tulassay, P Miheller, K Palatka, T Szamosi, S Fischer, J Papp, , M Papp
Antibodies against different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn's disease (CD). Recently, an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in various genes other than NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients...
June 2008: Tissue Antigens
Petr Hruz, Lars Eckmann
PURPOSE OF REVIEW: The present review discusses the physiological functions of selected caspase recruitment domain (CARD)-containing sensor and adaptor proteins and their role in the pathogenesis of intestinal diseases. RECENT FINDINGS: Myeloid and lymphoid cells as well as intestinal epithelial cells express several intracellular CARD-containing proteins. CARD-containing sensors, particularly NOD1 (CARD4), NOD2 (CARD15) and IPAF (CARD12), have an important role in the detection of conserved microbial structures of invading microbial pathogens...
March 2008: Current Opinion in Gastroenterology
R K Weersma, H M van Dullemen, G van der Steege, I M Nolte, J H Kleibeuker, G Dijkstra
INTRODUCTION: Inflammatory bowel disease (IBD) comprising ulcerative colitis (UC) and Crohn's disease (CD) is multigenic disorder. Tremendous progress has been achieved in unravelling the genetic background of IBD. It has led to the discovery of mutations in NOD2 associated with ileal CD and numerous other genes have been found to be associated with IBD susceptibility. METHODS: A review of the literature on the genetic background of IBD was performed. RESULTS: It is only partially understood how mutations in NOD2 lead to CD...
December 2007: Alimentary Pharmacology & Therapeutics
T Molnar, P Hofner, F Nagy, P L Lakatos, S Fischer, L Lakatos, A Kovacs, I Altorjay, M Papp, K Palatka, P Demeter, Z Tulassay, T Nyari, P Miheller, J Papp, Y Mandi, J Lonovics et al.
BACKGROUND: NOD1/CARD4, a member of the pattern-recognition receptor family, is a perfect candidate as a susceptibility gene for Crohn's disease. Since only limited and conflicting data are available on G796A polymorphisms in inflammatory bowel disease patients, we set out to study the effect of this polymorphism on the susceptibility and course of Crohn's disease in the Hungarian population. METHODS: Four hundred thirty-four unrelated Crohn's disease patients (age at presentation: 28...
December 2007: Digestive and Liver Disease
Lorena Rodriguez-Bores, Gabriela-C Fonseca, Marco-A Villeda, Jesus-K Yamamoto-Furusho
Genetic factors play a significant role in determining inflammatory bowel disease (IBD) susceptibility. Epidemiologic data support genetic contribution to the pathogenesis of IBD, which include familial aggregation, twin studies, racial and ethnic differences in disease prevalence. Linkage studies have identified several susceptibility genes contained in different genomic regions named IBD1 to IBD9. Nucleotide oligomerization domain (NOD2) and human leukocyte antigen (HLA) genes are the most extensively studied genetic regions (IBD1 and IBD3 respectively) in IBD...
November 14, 2007: World Journal of Gastroenterology: WJG
Filippina Macaluso, Michael Nothnagel, Qumar Parwez, Elisabeth Petrasch-Parwez, Falk Georges Bechara, Joerg Thomas Epplen, Sabine Hoffjan
Atopic dermatitis (AD) is a chronic skin disease affecting up to 15% of children in industrialized countries. AD belongs to the group of atopic disorders characterized by excessive immune reactions to ubiquitous antigens. Complex interactions between genetic and environmental factors have been suggested for atopic disorders. Dysregulation of the innate immune system appears crucial for the pathogenesis of AD. The NACHT-LRRs (NLRs) represent a group of innate immune receptors with special relevance for inflammatory processes...
August 2007: Experimental Dermatology
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