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NLRP3 inflammasome

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https://www.readbyqxmd.com/read/29224086/role-of-nlrp3-inflammasome-in-the-pathogenesis-of-cardiovascular-diseases
#1
REVIEW
Dongling Liu, Xiang Zeng, Xiao Li, Jawahar L Mehta, Xianwei Wang
NLRP3 inflammasome is a key multiprotein signaling platform that tightly controls inflammatory responses and coordinates antimicrobial host defenses by activating caspase-1 for the subsequent maturation of pro-inflammatory cytokines, IL-1β and IL-18, and induces pyroptosis. The assembly and activation of NLRP3 inflammasome are linked to the pathogenesis of several cardiovascular disease risk factors, such as hypertension and diabetes, and their major consequences-myocardial remodeling. The study of the NLRP3 inflammasome in these cardiovascular disease states may uncover important triggers and endogenous modulators of the disease, and lead to new treatment strategies...
December 9, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29222907/the-ameliorative-effect-of-fluoxetine-on-neuroinflammation-induced-by-sleep-deprivation
#2
Maosheng Xia, Xiaowei Li, Li Yang, Jiaan Ren, Guangfeng Sun, Shuang Qi, Alexei Verkhratsky, Baoman Li
It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29219210/bioenergetic-regulation-of-microglia
#3
REVIEW
Soumitra Ghosh, Erika Castillo, Elma S Frias, Raymond A Swanson
Microglia have diverse actions, ranging from synapse pruning in development to cytotoxic effects in disease. Brain energy metabolism and substrate availability vary under normal and disease states, but how these variations influence microglial function is relatively unknown. Microglia, like most other cell types, express the full complement of gene products required for both glycolytic and oxidative metabolism. Evidence suggests that microglia increase aerobic glycolysis and decrease respiration when activated by various stimuli...
December 8, 2017: Glia
https://www.readbyqxmd.com/read/29214547/association-of-nlrp3-polymorphisms-with-susceptibility-to-primary-gouty-arthritis-in-a-chinese-han-population
#4
Quan-Bo Zhang, Yu-Feng Qing, Yong-Long He, Wen-Guang Xie, Jing-Guo Zhou
The NLRP3-interleukin1β (IL1β) signaling pathway is involved in monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether single nucleotide polymorphisms (SNPs) in the NLRP3 gene are associated with susceptibility to gouty arthritis (GA) and whether these SNPs alter the expression of components of the NLRP3-IL1β signaling pathway. The rs10754558, rs4612666, and rs1539019 SNPs were detected in 583 patients with GA and 459 healthy subjects. NLRP3 and IL1β mRNA levels in peripheral blood mononuclear cells (PBMCs) and serum IL1β levels were measured in different genotype carriers, and correlations between the NLRP3 SNPs and NLRP3 mRNA, IL1β mRNA, and serum IL1β levels were investigated...
December 7, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29212744/selective-nlrp3-pyrin-domain-containing-protein-3-inflammasome-inhibitor-reduces-brain-injury-after-intracerebral-hemorrhage
#5
Honglei Ren, Ying Kong, Zhijia Liu, Dongyun Zang, Xiaoxia Yang, Kristofer Wood, Minshu Li, Qiang Liu
BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. As a key component of the innate immune system, the NOD-like receptor (NLR) family, NLRP3 (pyrin domain-containing protein 3) inflammasome, when activated after ICH, promotes neuroinflammation and brain edema. MCC950 is a potent, selective, small-molecule NLRP3 inhibitor that blocks NLRP3 activation at nanomolar concentrations. Here, we examined the effect of MCC950 on brain injury and inflammation in 2 models of ICH in mice...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29212498/salvianolic-acid-b-protects-against-lipopolysaccharide-induced-behavioral-deficits-and-neuroinflammatory-response-involvement-of-autophagy-and-nlrp3-inflammasome
#6
Pei Jiang, Yujin Guo, Ruili Dang, Mengqi Yang, Dehua Liao, Huande Li, Zhen Sun, Qingyan Feng, Pengfei Xu
BACKGROUND: The NLRP3 inflammasome activation and neuroinflammation are known to be involved in the pathology of depression, whereas autophagy has multiple effects on immunity, which is partly mediated by the regulation of inflammasome and clearance of proinflammatory cytokines. Given the emerging evidence that autophagy dysfunction plays an essential role in depression, it is very likely that autophagy may interact with the inflammatory process in the development and treatment of depression...
December 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29209318/the-major-chromoblastomycosis-etiologic-agent-fonsecaea-pedrosoi-activates-the-nlrp3-inflammasome
#7
Raffael Júnio Araújo de Castro, Isaque Medeiros Siqueira, Márcio Sousa Jerônimo, Angelina Maria Moreschi Basso, Paulo Henrique de Holanda Veloso Junior, Kelly Grace Magalhães, Luiza Chaves Leonhardt, Stephan Alberto Machado de Oliveira, Pedro Henrique Bürgel, Aldo Henrique Tavares, Anamélia Lorenzetti Bocca
Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of F. pedrosoi. Recently, we have shown that unlike conidia, hyphae and muriform cells (the parasitic morphotype) of F. pedrosoi promotes an intense inflammatory response pattern in vivo, which comprises the production of an inflammasome-derived cytokine, IL-1β...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29209310/alum-activates-the-bovine-nlrp3-inflammasome
#8
Ciaran Harte, Aoife L Gorman, S McCluskey, Michael Carty, Andrew G Bowie, C J Scott, Kieran G Meade, Ed C Lavelle
There has been a move away from vaccines composed of whole or inactivated antigens toward subunit-based vaccines, which although safe, provide less immunological protection. As a result, the use of adjuvants to enhance and direct adaptive immune responses has become the focus of much targeted bovine vaccine research. However, the mechanisms by which adjuvants work to enhance immunological protection in many cases remains unclear, although this knowledge is critical to the rational design of effective next generation vaccines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29207644/protection-by-simvastatin-on-hyperglycemia-induced-endothelial-dysfunction-through-inhibiting-nlrp3-inflammasomes
#9
Zhen-Huan Lv, Trinh Anh Phuong, Shi-Jie Jin, Xiao-Xue Li, Ming Xu
Recent studies have demonstrated that NLRP3 inflammasome complex acts as pivotal elements to initiate inflammatory responses and plays an important role in the dysfunction of cardiovascular complications. Meanwhile, simvastatin prevents vascular endothelial dysfunction from inflammasome invasion contributing to reduce cardiovascular risk. However, Whether or not the simvastatin improves vascular endothelial barrier function through inhibiting the activation of NLRP3 inflammasome pathway remains unknown. Here, we explored the role and mechanisms of simvastatin in the activation of NLRP3 inflammasome which are involved in vascular endothelial hyperpermeability causing by the disruption of tight junction protein ZO-1 and adherens junction protein VE-Cadherin, an early initiation of cardiovascular complication...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207123/nacht-lrr-and-pyd-domains-containing-protein-3-inflammasome-is-activated-and-inhibited-by-berberine-via-toll-like-receptor-4-myeloid-differentiation-primary-response-gene-88-nuclear-factor-%C3%AE%C2%BAb-pathway-in-phorbol-12-myristate-13-acetate-induced-macrophages
#10
Zhouqing Huang, Bozhi Ye, Jibo Han, Fanqi Kong, Peiren Shan, Zhongqiu Lu, Zhouqing Huang, Weijian Huang
The nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3) inflammasome has recently emerged as a pivotal regulator of chronic inflammation. The present study investigated the expression of NLRP3 inflammasome in phorbol 12-myristate 13-acetate (PMA)-induced macrophages, and aimed to identify the effects of berberine on the inflammasome. Human monocytic THP-1 cells were pretreated with berberine for 1 h and then induced with PMA for 48 h. Total RNA and protein were collected for reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively...
November 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29207030/der-f1-induces-pyroptosis-in-human-bronchial-epithelia-via-the-nlrp3-inflammasome
#11
Ying-Ming Tsai, Kuo-Hwa Chiang, Jen-Yu Hung, Wei-An Chang, Hui-Ping Lin, Jiunn-Min Shieh, Inn-Wen Chong, Ya-Ling Hsu
Damage to the bronchial epithelium leads to persistent inflammation and airway remodelling in various respiratory diseases, such as asthma and chronic obstructive pulmonary disease. To date, the mechanisms underlying bronchial epithelial cell damage and death by common allergens remain largely unknown. The aim of the present study was to investigate Der f1, an allergen of Dermatophagoides farinae, which may result in the death of human bronchial epithelial cells (HBECs). Der f1 induces BECs to undergo the inflammatory cell death referred to as pyroptosis, induced by increasing lactate dehydrogenase release and propidium iodide penetration...
December 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29203400/decreased-nlrp3-inflammasome-expression-in-aged-lung-may-contribute-to-increased-susceptibility-to-secondary-streptococcus-pneumoniae-infection
#12
Soo Jung Cho, Maria Plataki, Dana Mitzel, Gena Lowry, Kristen Rooney, Heather Stout-Delgado
Post-viral pneumococcal pneumonia is a leading morbidity and mortality in older patients (≥65years of age). The goal of our current study is to understand the impact of chronological aging on innate immune responses to a secondary, post viral infection with Streptococcus pneumoniae, a causative agent of bacterial pneumonia. Using aged murine models of infection, our findings demonstrate increased morbidity and mortality in aged mice within 48h post-secondary S. pneumoniae infection. Increased susceptibility of aged mice was associated with decreased TLR1, TLR6, and TLR9 mRNA expression and diminished IL1β mRNA expression...
December 1, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29203171/the-nlrp3-inflammasome-renders-cell-death-pro-inflammatory
#13
REVIEW
Moritz M Gaidt, Veit Hornung
NLRP3 is the most studied inflammasome sensor due to its crucial involvement in sterile and infection-triggered inflammation. Although its molecular mode of activation remains to be defined, it is well established that low intracellular potassium concentrations result in its activation. This functionality allows the classical NLRP3 pathway to serve as a highly sensitive, but non-specific surveillance mechanism responding to any type of perturbation that breaches plasma membrane integrity and the associated potassium-gradient across the membrane...
December 1, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29202301/spleen-tyrosine-kinase-inhibition-ameliorates-airway-inflammation-through-modulation-of-nlrp3-inflammosome-and-th17-treg-axis
#14
Divyesh Patel, Sagar Gaikwad, Naveen Challagundla, Manish Nivsarkar, Reena Agrawal-Rajput
Repeated exposure to the fungal pathogen Aspergillus fumigates triggers spleen tyrosine kinase (SYK) signalling through dectin-1 activation, which is associated with deleterious airway inflammation. β-Glucan-induced dectin-1 signalling activates the NLRP3 inflammasome, which in turn rapidly produces IL-1β, a master regulator of inflammation. IL-1β expression results in Th17/Treg imbalance, pulmonary inflammation, and bystander tissue injury. This study reports that 3,4 methylenedioxy-β-nitrostyrene (MNS), a potent SYK inhibitor, markedly decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines in vitro...
December 1, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29202274/red-raspberries-suppress-nlrp3-inflammasome-and-attenuate-metabolic-abnormalities-in-diet-induced-obese-mice
#15
Mei-Jun Zhu, Yifei Kang, Yansong Xue, Xingwei Liang, Melisa Paola González García, Dan Rodgers, Denali R Kagel, Min Du
The NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a critical role in insulin resistance and the pathogenesis of type 2 diabetes. Red raspberry (RB) contains high amounts of dietary fibers and polyphenolic compounds, which are known for their anti-oxidative and anti-inflammatory effects. This study evaluated the preventive effects of RB supplementation on the NLRP3 inflammasome activation and associated metabolic abnormalities induced by high fat diet (HFD). Wild-type male mice (six weeks old) were randomized into 4 groups receiving a control or typical western HFD supplemented with or without 5% freeze-dried RB for 12 weeks, when mice were sacrificed for tissue collection...
November 2, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29198726/neopterin-preconditioning-prevents-inflammasome-activation-in-mammalian-astrocytes
#16
Roberta de Paula Martins, Karina Ghisoni, Chai K Lim, Aderbal Silva Aguiar, Gilles J Guillemin, Alexandra Latini
Neopterin, a well-established biomarker for immune system activation, is found at increased levels in the cerebrospinal fluid of individuals affected by neurological/neurodegenerative diseases. Here, neopterin synthesis was investigated in different nerve cells (rodent and human) and in the mouse hippocampus under inflammatory stimuli. We also aimed to investigate whether neopterin preconditioning could modulate the inflammasome activation, a component of the innate immune system. Increased neopterin was detected in human nerve cells supernatants (highest secretion in astrocytes) exposed to lipopolysaccharide (LPS) and interferon-gamma (INF-γ) and in the hippocampus of mice receiving LPS (0...
November 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29196621/remodelling-of-the-gut-microbiota-by-hyperactive-nlrp3-induces-regulatory-t-cells-to-maintain-homeostasis
#17
Xiaomin Yao, Chenhong Zhang, Yue Xing, Guang Xue, Qianpeng Zhang, Fengwei Pan, Guojun Wu, Yingxin Hu, Qiuhong Guo, Ailing Lu, Xiaoming Zhang, Rongbin Zhou, Zhigang Tian, Benhua Zeng, Hong Wei, Warren Strober, Liping Zhao, Guangxun Meng
Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but the role of NLRP3 inflammasome in these processes is not well understood. Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have autoinflammation in skin, joints, and eyes, but not in the intestine. Here we show that the intestines of CAPS model mice carrying an Nlrp3 R258W mutation maintain homeostasis in the gut. Additionally, such mice are strongly resistant to experimental colitis and colorectal cancer; this is mainly through a remodelled gut microbiota with enhanced anti-inflammatory capacity due to increased induction of regulatory T cells (Tregs)...
December 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29196167/cathepsin-b-links-oxidative-stress-to-the-activation-of-nlrp3-inflammasome
#18
Hua Bai, Bo Yang, Wenfeng Yu, Yan Xiao, Dejun Yu, Qifang Zhang
Oxidative stress-mediated activation of NLRP3 inflammasome in microglia is critical in the development of neurodegerative diseases such as Alzheimer's disease (AD), Parkinson disease (PD). However, the mechanism underlying oxidative stress activates NLRP3 inflammasome remains exclusive. Here we demonstrated cathepsin B (CTSB) as a regulator of the activation of NLRP3 inflammasome by H2O2. H2O2 induced IL-1β secretion in NLRP3 inflammasome-dependent manner. H2O2 treatment increased CTSB activity, which in turn activated NLRP3 inflammasome, and subsequently processed pro-caspase-1 cleavage into caspase-1, resulting in IL-1 β secretion...
November 28, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29195923/calcific-tendonitis-of-the-rotator-cuff-from-formation-to-resorption
#19
Christelle Darrieutort-Laffite, Frédéric Blanchard, Benoit Le Goff
Calcific tendonitis of the rotator cuff is due to apatite deposits in the shoulder tendons. Patients affected by calcific tendonitis have chronic shoulder pain and disability. Although the disease is frequent, about 10 to 42% of painful shoulders, mechanisms leading to this pathological mineralization are still largely unknown. Research reported in the 90s suggested that the formation of calcific deposits is linked to cells looking like chondrocytes identified around calcium deposits within a fibrocartilage area...
November 28, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29193391/dihydromyricetin-inhibits-nlrp3-inflammasome-dependent-pyroptosis-by-activating-the-nrf2-signaling-pathway-in-vascular-endothelial-cells
#20
Qin Hu, Ting Zhang, Long Yi, Xi Zhou, Mantian Mi
Increasing evidence demonstrates that pyroptosis, pro-inflammatory programmed cell death, is linked to atherosclerosis; however, the underlying mechanisms remain to be elucidated. Dihydromyricetin (DHM), a natural flavonoid, was reported to exert anti-oxidative and anti-inflammatory bioactivities. However, the effect of DHM on atherosclerosis-related pyroptosis has not been studied. In the present study, palmitic acid (PA) treatment led to pyroptosis in human umbilical vein endothelial cells (HUVECs), as evidenced by caspase-1 activation, LDH release, and propidium iodide-positive staining; enhanced the maturation and release of proinflammatory cytokine IL-1β and activation of the NLRP3 inflammasome; and markedly increased intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS) levels...
November 29, 2017: BioFactors
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