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Margaret H Ainslie-Garcia, Abdolvahab Farzan, Mohsen Jafarikia, Brandon N Lillie
Foodborne human salmonellosis is an important food safety concern worldwide. Food-producing animals are one of the major sources of human salmonellosis, and thus control of Salmonella at the farm level could reduce Salmonella spread in the food supply system. Genetic selection of pigs with resistance to Salmonella infection may be one way to control Salmonella on swine farms. The objective of this study was to investigate the association between genetic variants in the porcine innate immune system with on-farm Salmonella shedding and Salmonella colonization tested at slaughter...
June 2018: Veterinary Microbiology
Xiaowei Wang, Haiying Jin, Shifeng Jiang, Yanlan Xu
Background: MicroRNAs (miRNAs) have physiological and pathophysiological functions that are involved in the regulation of cardiac fibrosis. This study aimed to investigate the effects of miR-495 on high glucose-induced cardiac fibrosis in human cardiac fibroblasts (CFs) and to establish the mechanism underlying these effects. Methods: Human CFs were transfected with an miR-495 inhibitor or mimic and incubated with high glucose. The levels of NOD1 and miR-495 were then determined via quantitative RT-PCR...
2018: Cellular & Molecular Biology Letters
Jun Gu, Gang Liu, Junjie Xing, Haihan Song, Zhongchuan Wang
Crohn's disease (CD) is characterized by a pathogenic intestinal inflammation mediated by a Th1-skewed immune system and a dysregulated intestinal mucosal community. In this study, we investigated the role of bacteria on the activation and function of monocytes, and its association with CD pathogenesis. To this end, fecal bacteria from CD patients and healthy controls were collected and used to stimulate autologous circulating monocytes. Fecal bacteria from CD patients were more effective at upregulating NOD2, NLRP3, TLR2, and TLR4 expression than fecal bacteria from healthy controls...
May 9, 2018: Microbial Pathogenesis
Nina Schmolka, Pedro H Papotto, Paula Vargas Romero, Tiago Amado, Francisco J Enguita, Ana Amorim, Ana F Rodrigues, Katrina E Gordon, Ana S Coroadinha, Mark Boldin, Karine Serre, Amy H Buck, Anita Q Gomes, Bruno Silva-Santos
γδ T cells are major providers of proinflammatory cytokines. They are preprogrammed in the mouse thymus into distinct subsets producing either interleukin-17 (IL-17) or interferon-γ (IFN-γ), which segregate with CD27 expression. In the periphery, CD27- γδ (γδ27- ) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-γ; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in γδ T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-γ expression in γδ27- T cells in vitro and in vivo...
May 4, 2018: Science Immunology
Anutosh Paria, M Makesh, Aparna Chaudhari, C S Purushothaman, K V Rajendran
NOD1 (Nucleotide-binding oligomerization domain-containing protein 1) is one of the most prominent intracellular Nod-like receptors (NLRs), responsible for detecting different microbial components and products arising from tissue injury. Here, we have identified and cloned NOD1 transcript in the Asian seabass, Lates calcarifer (AsNOD1), which consists of 3749 nucleotides and encodes for a predicted putative protein of 900 AA. The AsNOD1 possesses the typical structure of NLR family, consisting of N-terminal CARD domain, centrally located NACHT domain and C-terminal LRRs...
April 30, 2018: Fish & Shellfish Immunology
Kosuke Minaga, Tomohiro Watanabe, Ken Kamata, Naoki Asano, Masatoshi Kudo
Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori ( H. pylori ) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer...
April 28, 2018: World Journal of Gastroenterology: WJG
Xiao Man Wu, Wen Qin Chen, Yi Wei Hu, Lu Cao, Pin Nie, Ming Xian Chang
RIP2 is an adaptor protein which is essential for the activation of NF-κB and NOD1- and NOD2-dependent signaling. Although NOD-RIP2 axis conservatively existed in the teleost, the function of RIP2 was only reported in zebrafish, goldfish, and rainbow trout in vitro . Very little is known about the role and mechanisms of piscine NOD-RIP2 axis in vivo . Our previous study showed the protective role of zebrafish NOD1 in larval survival through CD44a-mediated activation of PI3K-Akt signaling. In this study, we examined whether RIP2 was required for larval survival with or without pathogen infection, and determined the signaling pathways modulated by RIP2...
2018: Frontiers in Immunology
Yuhui Ouyang, Zhaojun Xu, Erzhong Fan, Ying Li, Kunio Miyake, Xianyan Xu, Luo Zhang
Particulate matter (PM) air pollution has been associated with an increase in the incidence of chronic allergic diseases; however, the mechanisms underlying the effect of exposure to natural ambient air pollution in chronic allergic diseases have not been fully elucidated. In the present study, we aimed to investigate the cellular responses induced by exposure to natural ambient air pollution, employing a mouse model of chronic allergy. The results indicated that exposure to ambient air pollution significantly increased the number of eosinophils in the nasal mucosa...
April 20, 2018: Scientific Reports
Walter R Drake, Ching-Wen Hou, Natasha E Zachara, Catherine Leimkuhler Grimes
O-GlcNAcylation is a dynamic and functionally diverse post-translational modification shown to affect thousands of proteins, including the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (Nod2). Mutations of Nod2 (R702W, G908R and 1007 fs) are associated with Crohn's disease and have lower stabilities compared to wild type. Cycloheximide (CHX)-chase half-life assays have been used to show that O-GlcNAcylation increases the stability and response of both wild type and Crohn's variant Nod2, R702W...
April 18, 2018: Journal of Bioenergetics and Biomembranes
María-Alexandra Cañas, María-José Fábrega, Rosa Giménez, Josefa Badia, Laura Baldomà
Gut microbiota plays a critical role in maintaining human intestinal homeostasis and host health. Bacterial extracellular vesicles are key players in bacteria-host communication, as they allow delivery of effector molecules into the host cells. Outer membrane vesicles (OMVs) released by Gram-negative bacteria carry many ligands of pattern recognition receptors that are key components of innate immunity. NOD1 and NOD2 cytosolic receptors specifically recognize peptidoglycans present within the bacterial cell wall...
2018: Frontiers in Microbiology
Fernando J Velloso, Mari Cleide Sogayar, Ricardo G Correa
OBJECTIVE: Immune-related pathways have been frequently associated to tumorigenesis. NOD1 and NOD2 are innate immune receptors responsible for sensing a subset of bacterial-derived components, and to further translate these pathogenic signals through pro-inflammatory and survival pathways. NOD1 and NOD2 have been further associated with tumorigenesis, particularly in gastrointestinal cancers. NOD1 has also been suggested to be a tumor suppressor gene in a model of estrogen receptor-dependent breast cancer...
April 3, 2018: BMC Research Notes
Ingrid Stroo, Diba Emal, Loes M Butter, Gwen J Teske, Nike Claessen, Mark C Dessing, Stephen E Girardin, Sandrine Florquin, Jaklien C Leemans
BACKGROUND: Chronic kidney disease (CKD) is characterized by sustained tissue damage and ongoing tubulo-interstitial inflammation and fibrosis. Pattern recognition receptors (PRRs) including Toll-like receptors (TLRs) and NOD-like receptors (NLRs) can sense endogenous ligands released upon tissue damage, leading to sterile inflammation and eventually irreversible kidney disease. It is known that NOD1 and NOD2 contribute to the pathogenesis of various inflammatory diseases, including acute kidney injury...
April 2, 2018: BMC Nephrology
Izortze Santin, Amaia Jauregi-Miguel, Teresa Velayos, Ainara Castellanos-Rubio, Koldo Garcia-Etxebarria, Irati Romero-Garmendia, Nora Fernandez-Jimenez, Iñaki Irastorza, Luis Castaño, Jose Ramón Bilbao
OBJECTIVE: To identify additional celiac disease associated loci in the Major Histocompatibility Complex independent from classical HLA risk alleles (HLA-DR3-DQ2) and to characterize their potential functional impact in celiac disease pathogenesis at the intestinal level. METHODS: We performed a high resolution SNP genotyping of the MHC region, comparing HLA-DR3 homozygous celiac patients and non-celiac controls carrying a single copy of the B8-DR3-DQ2 conserved extended haplotype...
March 29, 2018: Journal of Pediatric Gastroenterology and Nutrition
Shunmei Huang, Shi Zou, Mingfa Chen, Xiaoyan Gao, Liwen Chen, Xilang Yang, Qing Yu, Xiaoli Zhao, Yanqin Du, Xuecheng Yang, Yong Lin, Baoju Wang, Yinping Lu, Jia Liu, Xin Zheng, Feili Gong, Mengji Lu, Dongliang Yang, Jun Wu
Functional maturation of liver sinusoidal endothelial cells (LSECs) induced by a NOD1 ligand (diaminopimelic acid [DAP]) during viral infection has not been well defined. Thus, we investigated the role of DAP-stimulated LSEC maturation during hepatitis B virus (HBV) infection and its potential mechanism in a hydrodynamic injection (HI) mouse model. Primary LSECs were isolated from wild-type C57BL/6 mice and stimulated with DAP in vitro and in vivo and assessed for the expression of surface markers as well as for their ability to promote T cell responses via flow cytometry...
March 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Sajal Kole, Ranjeeta Kumari, Deepika Anand, Saurav Kumar, Rupam Sharma, Gayatri Tripathi, M Makesh, K V Rajendran, Megha Kadam Bedekar
DNA-based immunization has proven to be an effective prophylactic measure to control aquatic animal diseases. In order to improve the efficiency of vaccine against fish pathogen, novel delivery mechanism needs to be adopted. In the present study we nanoconjugated the previously constructed DNA vaccine (pGPD + IFN) with chitosan nanoparticles (CNPs) by complex coacervation process. After construction of the vaccine, an in vivo vaccination trial was conducted in which 2 groups of rohu (L. rohita) fingerlings were vaccinated with CNPs-pGPD + IFN, one group by oral route (incorporated in feed for 14 days) and the other by immersion route (primary and booster immunised), whereas, a third group was intramuscularly (I/M) injected (initial and booster immunised) with naked pGPD + IFN and subsequently challenged with E...
March 12, 2018: Vaccine
Huiling Zhu, Haibo Wang, Shuhui Wang, Zhixiao Tu, Lin Zhang, Xiuying Wang, Yongqing Hou, Chunwei Wang, Jie Chen, Yulan Liu
SCOPE: Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigates the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS). MATERIALS AND RESULTS: Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs 5% flaxseed oil) and LPS challenge (saline vs LPS)...
May 2018: Molecular Nutrition & Food Research
Gordon C Weir, Mario R Ehlers, Kristina M Harris, Sai Kanaparthi, Alice Long, Deborah Phippard, Lia J Weiner, Brett Jepson, James G McNamara, Maria Koulmanda, Terry B Strom
OBJECTIVE: To determine the safety and pharmacokinetics of alpha-1 antitrypsin (AAT) in adults and children. RESEARCH DESIGN AND METHODS: Short-term AAT treatment restores euglycemia in the non-obese mouse model of type 1 diabetes. A phase I multicenter study in 16 subjects with new-onset type 1 diabetes studied the safety and pharmacokinetics of Aralast NP (AAT). This open-label, dose-escalation study enrolled 8 adults aged 16 to 35 years and 8 children aged 8 to 15 years within 100 days of diagnosis, to receive 12 infusions of AAT: a low dose of 45 mg/kg weekly for 6 weeks, followed by a higher dose of 90 mg/kg for 6 weeks...
February 23, 2018: Pediatric Diabetes
Josiane V Cruz, Moysés F A Neto, Luciane B Silva, Ryan da S Ramos, Josivan da S Costa, Davi S B Brasil, Cleison C Lobato, Glauber V da Costa, José Adolfo H M Bittencourt, Carlos H T P da Silva, Franco H A Leite, Cleydson B R Santos
The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, including sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2 is an affinity strategy that demonstrates an increased expression of pro-inflammatory secretion activity. In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built...
February 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Fabiane Sônego, Fernanda V S Castanheira, Catarina V Horta, Alexandre Kanashiro, Paula G Czaikoski, Dario S Zamboni, José Carlos Alves-Filho, Fernando Q Cunha
OBJECTIVE AND DESIGN: The objective of this study was to investigate the role of Nod1 in the recruitment of neutrophils into the infection site and in the establishment of the inflammatory response elicited by a clinical isolate strain of P. aeruginosa in vivo, while comparing it to the well-established role of MyD88 in this process. SUBJECTS: Wild-type, Nod1-/- and MyD88-/- mice, all with a C57Bl/6 background. METHODS: Mice were intranasally infected with Pseudomonas aeruginosa DZ605...
May 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Jinxiang Liu, Dandan Cao, Yuezhong Liu, Zan Li, Yu Si, Zhigang Wang, Quanqi Zhang, Haiyang Yu, Xubo Wang
Being a key adaptor protein in NOD1/2 and NF-κB signaling pathways, receptor-interacting serine/threonine kinase 2 (RIP2) plays an important role in innate immune response in vertebrates. In this study, we identified and characterized the Paralichthys olivaceus RIP2 gene (PoRIP2). Phylogenetic, alignment, and genomic analysis of PoRIP2 were conducted to determine its conservation and evolutionary relationship with other RIP2 in vertebrates. qRT-PCR results showed that the expression of PoRIP2 was high in the spleen and head kidney...
April 2018: Fish & Shellfish Immunology
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