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NLRP12

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https://www.readbyqxmd.com/read/27800616/nlrp12-negatively-regulates-proinflammatory-cytokine-production-and-host-defense-against-brucella-abortus
#1
Tatiana N Silveira, Marco Túlio R Gomes, Luciana S Oliveira, Priscila C Campos, Gabriela G Machado, Sergio C Oliveira
Brucella abortus is the causative agent of brucellosis, which causes abortion in domestic animals and undulant fever in humans. This bacterium infects and proliferates mainly in macrophages and dendritic cells, where it is recognized by pattern recognition receptors (PRRs) including Nod-like receptors (NLRs). Our group recently demonstrated the role of AIM2 and NLRP3 in Brucella recognition. Here, we investigated the participation of NLRP12 in innate immune response to B. abortus. We show that NLRP12 inhibits the early production of IL-12 by bone marrow-derived macrophages upon B...
November 1, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27788256/p2y1-receptor-signaling-contributes-to-high-salt-induced-priming-of-the-nlrp3-inflammasome-in-retinal-pigment-epithelial-cells
#2
Philipp Prager, Margrit Hollborn, Anja Steffen, Peter Wiedemann, Leon Kohen, Andreas Bringmann
BACKGROUND: Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCl-induced NLRP3 gene expression...
2016: PloS One
https://www.readbyqxmd.com/read/27779193/nlrp12-mutation-causes-c57bl-6j-strain-specific-defect-in-neutrophil-recruitment
#3
Tyler K Ulland, Nidhi Jain, Emma E Hornick, Eric I Elliott, Gwendolyn M Clay, Jeffrey J Sadler, Kathleen A M Mills, Ann M Janowski, A Paige Davis Volk, Kai Wang, Kevin L Legge, Lokesh Gakhar, Mohammed Bourdi, Polly J Ferguson, Mary E Wilson, Suzanne L Cassel, Fayyaz S Sutterwala
The inbred mouse strain C57BL/6J is widely used in models of immunological and infectious diseases. Here we show that C57BL/6J mice have a defect in neutrophil recruitment to a range of inflammatory stimuli compared with the related C57BL/6N substrain. This immune perturbation is associated with a missense mutation in Nlrp12 in C57BL/6J mice. Both C57BL/6J and NLRP12-deficient mice have increased susceptibility to bacterial infection that correlates with defective neutrophil migration. C57BL/6J and NLRP12-deficient macrophages have impaired CXCL1 production and the neutrophil defect observed in C57BL/6J and NLRP12-deficient mice is rescued by restoration of macrophage NLRP12...
October 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27716579/the-transcription-factor-nuclear-factor-erythroid-2-nfe2-is-a-regulator-of-the-oxidative-stress-response-during-danio-rerio-development
#4
Larissa M Williams, Briony A Lago, Andrew G McArthur, Amogelang R Raphenya, Nicholas Pray, Nabil Saleem, Sophia Salas, Katherine Paulson, Roshni S Mangar, Yang Liu, Andy H Vo, Jordan A Shavit
Development is a complex and well-defined process characterized by rapid cell proliferation and apoptosis. At this stage in life, a developmentally young organism is more sensitive to toxicants as compared to an adult. In response to pro-oxidant exposure, members of the Cap'n'Collar (CNC) basic leucine zipper (b-ZIP) transcription factor family (including Nfe2 and Nfe2-related factors, Nrfs) activate the expression of genes whose protein products contribute to reduced toxicity. Here, we studied the role of the CNC protein, Nfe2, in the developmental response to pro-oxidant exposure in the zebrafish (Danio rerio)...
October 1, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27633793/nlrp12-autoinflammatory-disease-a-chinese-case-series-and-literature-review
#5
Min Shen, Lin Tang, Xiaochun Shi, Xiaofeng Zeng, Qingping Yao
As one of the systemic autoinflammatory diseases (SAIDs), the nucleotide-binding oligomerization domain-like receptor protein (NLRP)12 autoinflammatory disease (NLRP12-AD) is an autosomal dominant disorder associated with NLRP12 mutation. SAIDs have been hardly reported in the Chinese population, and NLRP12-AD has been reported only in Caucasians. We report the first case series of NLRP12-AD in the Chinese population coupled with literature review. Three Han Chinese adult patients with clinical phenotype suggestive of NLRP12-AD carrying NLRP12 variants were treated by the authors in 2015...
September 16, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27585668/understanding-chemical-allergen-potency-role-of-nlrp12-and-blimp-1-in-the-induction-of-il-18-in-human-keratinocytes
#6
Angela Papale, Elena Kummer, Valentina Galbiati, Marina Marinovich, Corrado L Galli, Emanuela Corsini
Keratinocytes (KCs) play a key role in all phases of skin sensitization. We recently identified interleukin-18 (IL-18) production as useful end point for determination of contact sensitization potential of low molecular weight chemicals. The aim of this study was to identify genes involved in skin sensitizer-induced inflammasome activation and to establish their role in IL-18 production. For gene expression analysis, cells were treated for 6 h with p-phenylenediamine (PPD) as reference contact allergen; total RNA was extracted and examined with a commercially available Inflammasome Polymerase Chain Reaction (PCR) array...
September 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27399967/meta-analysis-of-rare-and-common-exome-chip-variants-identifies-s1pr4-and-other-loci-influencing-blood-cell-traits
#7
(no author information available yet)
Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals (37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB)...
August 2016: Nature Genetics
https://www.readbyqxmd.com/read/27377055/involvement-of-egf-receptor-signaling-and-nlrp12-inflammasome-in-fine-particulate-matter-induced-lung-inflammation-in-mice
#8
Yuefei Jin, Weidong Wu, Weiguo Zhang, Yang Zhao, Yongjun Wu, Guoyin Ge, Yue Ba, Qiang Guo, Tianyu Gao, Xuejing Chi, Huiyun Hao, Jing Wang, Feifei Feng
Epidemiological studies have shown that exposure to ambient fine particulate matter (PM2.5 ) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM2.5 exposure. However, the mechanisms underlying PM2.5 -induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM2.5 -induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM2...
July 5, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27314497/identification-of-a-novel-nlrp12-nonsense-mutation-trp408x-in-the-extremely-rare-disease-fcas-by-exome-sequencing
#9
Xiaoru Xia, Caijun Dai, Xiaochun Zhu, Qiumei Liao, Xu Luo, Yangyang Fu, Liangxing Wang
Familial cold autoinflammatory syndrome (FCAS) is an extremely rare autosomal dominant inherited disease. Although there are four genes that have been linked with FCAS, its molecular diagnosis has been challenging in a relatively large proportion of cases. In this study, we aimed to investigate the genetic defect of a recruited FCAS family using exome sequencing followed by in-depth bioinformatics analysis. As a result, a novel heterozygous stop-gain mutation (Trp408X) in NLRP12 was identified in autosomal dominant inherited FCAS with clinical features of recurrent fever and skin urticaria due to cold conditions...
2016: PloS One
https://www.readbyqxmd.com/read/27221480/atypical-inflammasomes
#10
Ann M Janowski, Fayyaz S Sutterwala
Pattern recognition receptors, including members of the NLR and PYHIN families, are essential for recognition of both pathogen- and host-derived danger signals. A number of molecules in these families are capable of forming multiprotein complexes termed inflammasomes that result in the activation of caspase-1. In addition to NLRP1, NLRP3, NLRC4, and AIM2, which form well-described inflammasome complexes, IFI16, NLRP6, NLRP7, NLRP12, and NLRC5 have also been proposed to form inflammasomes under specific conditions...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27158778/association-of-egf-receptor-and-nlrs-signaling-with-cardiac-inflammation-and-fibrosis-in-mice-exposed-to-fine-particulate-matter
#11
Yuefei Jin, Zhaoke Wu, Na Wang, Shuyin Duan, Yongjun Wu, Jing Wang, Weidong Wu, Feifei Feng
ЄAmbient fine particulate matter (PM2.5 ) could induce cardiovascular diseases (CVD), but the mechanism remains unknown. To investigate the roles of epidermal growth factor receptor (EGFR) and NOD-like receptors (NLRs) in PM2.5 -induced cardiac injury, we set up a BALB/c mice model of PM2.5 -induced cardiac inflammation and fibrosis with intratracheal instillation of PM2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days (once per day). After exposure, we found that mRNA levels of CXCL1, interleukin (IL)-6, and IL-18 were elevated, but interestingly, mRNA level of NLRP12 was significant decreased in heart tissue from PM2...
September 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27105524/inflammasome-independent-role-of-nlrp12-in-suppressing-colonic-inflammation-regulated-by-blimp-1
#12
Fushan Shi, Yang Yang, Mohammed Kouadir, Wei Xu, Songhua Hu, Tiancheng Wang
NLRP12 is a member of the Nod-like receptor (NLR). Previous studies have reported enhanced colitis-associated inflammatory responses in NLRP12-deficient mice. In this study, we sought to investigate the role of NLRP12 in DSS-stimulated proinflammatory response in dendritic cells and mice colitis, and the molecular mechanisms involved in the development of the inflammation. Our results showed that down-regulation of NLRP12 is required for DSS-induced release of proinflammatory cytokines IL-1β and TNF-α; that PR domain zinc finger protein 1 (also known as Blimp-1) induces NLRP12 down-regulation during DSS-induced proinflammatory response and colitis; and that TLR4 is implicated in the up-regulation of Blimp-1 that led to the down-regulation of NLRP12 expression in DSS-induced colitis...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/26946405/contribution-of-inflammasome-genetics-in-plasmodium-vivax-malaria
#13
Marina L S Santos, Edione Cristina Reis, Pamela N Bricher, Tais N Sousa, Cristiana F A Brito, Marcus V G Lacerda, Cor J F Fontes, Luzia H Carvalho, Alessandra Pontillo
Recent reports showed that, in mice, symptomatic Plasmodium infection triggers NLRP3/NLRP12-dependent inflammasome formation and caspase-1 activation in monocytes. In humans, few works demonstrated that inflammasome is activated in malaria. As Plasmodiumvivax is a potent inducer of inflammatory response we hypothesised that inflammasome genetics might affect P. vivax malaria clinical presentation. For this purpose, selected SNPs in inflammasome genes were analysed among patients with symptomatic P. vivax malaria...
June 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/26763980/beyond-the-inflammasome-regulatory-nod-like-receptor-modulation-of-the-host-immune-response-following-virus-exposure
#14
REVIEW
Sheryl Coutermarsh-Ott, Kristin Eden, Irving Coy Allen
A complex interaction exists between elements of the host innate immune system and viral pathogens. It is essential that the host mount a robust immune response during viral infection and effectively resolve inflammation once the pathogen has been eliminated. Members of the nucleotide-binding domain leucine-rich repeat [NBD-LRR; known as NOD-like receptor (NLR)] family of cytosolic pattern-recognition receptors are essential components of these immunological processes and have diverse functions in the host antiviral immune response...
April 2016: Journal of General Virology
https://www.readbyqxmd.com/read/26602157/manumycin-a-downregulates-release-of-proinflammatory-cytokines-from-tnf-alpha-stimulated-human-monocytes
#15
Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Miroslav Petricek, Alena Sekerkova, Veronika Svachova, Ilja Striz
Macrolide antibiotics such as azithromycin or clarithromycin are known to have potent anti-inflammatory and immunomodulatory effects but these properties cannot be widely used due to a risk of bacterial resistance. We studied another polyketide antibiotic, structurally related manumycin A known as a streptomycete derived farnesyltransferase inhibitor with limited antibacterial effects, with respect to its potential regulation of mRNA expression of several genes associated with proinflammatory responses. Downregulation of mRNA for IL-6, TLR-8, IL-1 beta and IL-10 was found in THP-1 cells after 4h stimulation with TNF alpha in the presence of manumycin A and downregulated TLR-8 and EGR-1 genes were observed after 8h...
January 2016: Immunology Letters
https://www.readbyqxmd.com/read/26521018/the-nod-like-receptor-nlrp12-plays-an-anti-inflammatory-role-in-experimental-autoimmune-encephalomyelitis
#16
Marjan Gharagozloo, Tara M Mahvelati, Emilie Imbeault, Pavel Gris, Echarki Zerif, Diwakar Bobbala, Subburaj Ilangumaran, Abdelaziz Amrani, Denis Gris
BACKGROUND: Multiple sclerosis (MS) is an organ-specific autoimmune disease resulting in demyelinating plaques throughout the central nervous system. In MS, the exact role of microglia remains unknown. On one hand, they can present antigens, skew T cell responses, and upregulate the expression of pro-inflammatory molecules. On the other hand, microglia may express anti-inflammatory molecules and inhibit inflammation. Microglia express a wide variety of immune receptors such as nod-like receptors (NLRs)...
2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/26490556/the-potential-repertoire-of-the-innate-immune-system-in-the-bladder-expression-of-pattern-recognition-receptors-in-the-rat-bladder-and-a-rat-urothelial-cell-line-myp3-cells
#17
Francis M Hughes, David P Turner, J Todd Purves
PURPOSE: The urothelium is a frontline sensor of the lower urinary tract, sampling the bladder lumen and stimulating an immune response to infectious and noxious agents. Pattern recognition receptors (PRRs) recognize such agents and coordinate the innate response, often by forming inflammasomes that activate caspase-1 and the release of interleukin-1. We have shown the presence of one PRR (NLRP3) in the urothelia and its central role in the inflammatory response to cyclophosphamide. The purpose of this study was to (1) assess the likely range of the PPR response by assessing the repertoire present in the rat bladder and (2) determine the utility of the MYP3 rat urothelia cell line for in vitro studies by assessing its PPR repertoire and functional responsiveness...
December 2015: International Urology and Nephrology
https://www.readbyqxmd.com/read/26386126/next-generation-sequencing-and-its-initial-applications-for-molecular-diagnosis-of-systemic-auto-inflammatory-diseases
#18
Marta Rusmini, Silvia Federici, Francesco Caroli, Alice Grossi, Maurizia Baldi, Laura Obici, Antonella Insalaco, Alberto Tommasini, Roberta Caorsi, Eleonora Gallo, Alma Nunzia Olivieri, AngeloValerio Marzano, Domenico Coviello, Roberto Ravazzolo, Alberto Martini, Marco Gattorno, Isabella Ceccherini
OBJECTIVES: Systemic auto-inflammatory disorders (SAIDs) are a heterogeneous group of monogenic diseases sharing a primary dysfunction of the innate immune system. More than 50% of patients with SAID does not show any mutation at gene(s) tested because of lack of precise clinical classification criteria and/or incomplete gene screening. To improve the molecular diagnosis and genotype interpretation of SAIDs, we undertook the development of a next-generation sequencing (NGS)-based protocol designed to simultaneous screening of 10 genes...
August 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/26378020/expression-profile-of-innate-immune-receptors-nlrs-and-aim2-in-human-colorectal-cancer-correlation-with-cancer-stages-and-inflammasome-components
#19
Rongrong Liu, Agnieszka D Truax, Liang Chen, Peizhen Hu, Zengshan Li, Jun Chen, Chaojun Song, Lihua Chen, Jenny Pan-Yun Ting
NLRs (nucleotide-binding domain leucine-rich repeat proteins or NOD-like receptors) are regulators of inflammation and immunity. A subgroup of NLRs and the innate immune receptor, AIM2 (absent-in-melanoma 2), can induce the assembly of a large caspase-1 activating complex called the inflammasome. Other NLRs regulate key signaling pathways such as NF-kB and MAPK. Since inflammation is a central component of colorectal cancer (CRC), this work was undertaken to analyze NLR and AIM2 expression in human CRC by combining bioinformatics analysis and experimental verification using clinical tissue samples...
October 20, 2015: Oncotarget
https://www.readbyqxmd.com/read/26349659/nlrp12-modulates-host-defense-through-il-17a-cxcl1-axis
#20
S Cai, S Batra, F Del Piero, S Jeyaseelan
We used an extracellular pathogen Klebsiella pneumoniae to determine the role of NLRP12 (NOD-like receptor (NLR) family pyrin domain containing 12) as this bacterium is associated with devastating pulmonary infections. We found that human myeloid cells (neutrophils and macrophages) and non-myeloid cells (epithelial cells) show upregulation of NLRP12 in human pneumonic lungs. NLRP12-silenced human macrophages and murine Nlrp12(-/-) macrophages displayed reduced activation of nuclear factor-κB and mitogen-activated protein kinase, as well as expression of histone deacetylases following K...
March 2016: Mucosal Immunology
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