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NLRP3 inflammasome

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https://www.readbyqxmd.com/read/28544564/podocyte-activation-of-nlrp3-inflammasomes-contributes-to-the-development-of-proteinuria-in-lupus-nephritis
#1
Rong Fu, Chaohuan Guo, Shuang Wang, Yuefang Huang, Ou Jin, Haoqiang Hu, Jingxian Chen, Bihua Xu, Mianjing Zhou, Jijun Zhao, Sun-Sang J Sung, Hongyang Wang, Felicia Gaskin, Niansheng Yang, Shu-Man Fu
Objective Development of proteinuria in lupus nephritis (LN) is associated with podocyte dysfunction. The NLRP3 inflammasome has been implicated in the pathogenesis of LN. This study investigates whether NLRP3 inflammasome activation is involved in the development of podocyte injury in LN. Methods A fluorescence-labeled caspase-1 inhibitor probe was used to detect the activation of NLRP3 inflammasomes in podocytes in lupus-prone NZM2328 mice and in renal biopsies from LN patients. MCC950, a selective inhibitor of NLRP3, was used to treat NZM2328 mice...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28542146/the-role-of-extracellular-histone-in-organ-injury
#2
REVIEW
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28537251/antigen-specific-cd8-t-cell-feedback-activates-nlrp3-inflammasome-in-antigen-presenting-cells-through-perforin
#3
Yikun Yao, Siyuan Chen, Mengtao Cao, Xing Fan, Tao Yang, Yin Huang, Xinyang Song, Yongqin Li, Lilin Ye, Nan Shen, Yufang Shi, Xiaoxia Li, Feng Wang, Youcun Qian
The connection between innate and adaptive immunity is best exemplified by antigen presentation. Although antigen-presenting cells (APCs) are required for antigen receptor-mediated T-cell activation, how T-cells feedback to APCs to sustain an antigen-specific immune response is not completely clear. Here we show that CD8(+) T-cell (also called cytotoxic T lymphocytes, CTL) feedback activates the NLRP3 inflammasome in APCs in an antigen-dependent manner to promote IL-1β maturation. Perforin from antigen-specific CTLs is required for NLRP3 inflammasome activation in APCs...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536183/the-nlrp3-inflammasome-contributes-to-sarcopenia-and-lower-muscle-glycolytic-potential-in-old-mice
#4
Marin Jane McBride, Kevin P Foley, Donna M D'souza, Yujin E Li, Trevor C Lau, Thomas J Hawke, Jonathan D Schertzer
The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. "Inflammaging" - increased inflammation with advancing age - may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1 containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild type (WT) and NLRP3(-/-) mice were aged to 10 months (adult) and 24 months (old)...
May 23, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28533778/dnase1l3-regulates-inflammasome-dependent-cytokine-secretion
#5
Guilan Shi, Kennady N Abbott, Wenbo Wu, Russell D Salter, Peter A Keyel
Pediatric-onset systemic lupus erythematosus arises in humans and mice lacking the endonuclease Dnase1L3. When Dnase1L3 is absent, DNA from circulating apoptotic bodies is not cleared, leading to anti-DNA antibody production. Compared to early anti-DNA and anti-chromatin responses, other autoantibody responses and general immune activation in Dnase1L3(-/-) mice are greatly delayed. We investigated the possibility that immune activation, specifically inflammasome activation, is regulated by Dnase1L3. Here, we report that Dnase1L3 inhibition blocked both NLR family, pyrin domain containing 3 (NLRP3) and NLRC4 inflammasome-mediated release of high-mobility group box 1 protein and IL-1β...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28532818/tdp-43-upregulation-mediated-by-the-nlrp3-inflammasome-induces-cognitive-impairment-in-2-2-4-4-tetrabromodiphenyl-ether-bde-47-treated-mice
#6
Juan Zhuang, Xin Wen, Yan-Qiu Zhang, Qun Shan, Zi-Feng Zhang, Gui-Hong Zheng, Shao-Hua Fan, Meng-Qiu Li, Dong-Mei Wu, Bin Hu, Jun Lu, Yuan-Lin Zheng
It is now commonly known that exposure to polybrominated diphenyl ethers (PBDEs) may cause neurotoxicity and cognitive deficits in children as well as adults, but the underlying mechanisms are still not clear. In the present study, we aimed to elucidate the potential underlying mechanism of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity and cognitive impairment. Our results showed that BDE-47-treated mice exhibited impaired cognition and robust upregulation of nuclear TDP-43 in the hippocampus...
May 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28532674/cytokine-expression-levels-in-als-a-potential-link-between-inflammation-and-bmaa-triggered-protein-misfolding
#7
Nara Michaelson, Dominic Facciponte, Walter Bradley, Elijah Stommel
Recently, it has been shown that proinflammatory cytokines play a complex and important role in the pathogenesis of many neurological disorders, including amyotrophic lateral sclerosis (ALS). To help facilitate future discoveries and more effective treatment strategies, we highlight the role that both innate and adaptive immune systems play in ALS and summarize the main observations that relate to cytokine expression levels in this disease. Furthermore, we propose a mechanism by which a known neurotoxin, β-N-methylamino-l-alanine (BMAA), may trigger this cytokine expression profile through motor neuron protein misfolding and subsequent NLRP3 (nucleotide-binding domain (NOD)-like receptor protein 3) inflammasome activation...
May 10, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28528200/sputum-transcriptomics-reveal-up-regulation-of-il-1-receptor-family-members-in-severe-asthma
#8
Christos Rossios, Stelios Pavlidis, Uruj Hoda, Chih-Hsi Kuo, Coen Wiegman, Kirsty Russell, Kai Sun, Matthew J Loza, Frederic Baribaud, Andrew L Durham, Oluwaseun Ojo, Rene Lutter, Anthony Rowe, Aruna Bansal, Charles Auffray, Ana Sousa, Julie Corfield, Ratko Djukanovic, Yike Guo, Peter J Sterk, Kian Fan Chung, Ian M Adcock
BACKGROUND: Sputum analysis in asthma is used to define airway inflammatory processes and may guide therapy. OBJECTIVE: To determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared to mild-moderate non-smoking asthmatics (MMA). METHODS: Induced sputum was obtained from non-smoking SA (SAn), smokers/ex-smokers with SA (SAsm), MMA and healthy non-smoking controls. Differential cell counts, microarray analysis of cell pellets and SOMAscan analysis of sputum analytes was performed...
May 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28528118/calcium-supplementation-decreases-bcp-induced-inflammatory-processes-in-blood-cells-through-the-nlrp3-inflammasome-down-regulation
#9
Patricia Lagadec, Thierry Balaguer, Florian Boukhechba, Grégory Michel, Sébastien Bouvet-Gerbettaz, Jean-Michel Bouler, Jean-Claude Scimeca, Nathalie Rochet
Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28526339/magnesium-isoglycyrrhizinate-blocks-fructose-induced-hepatic-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-and-lipid-metabolism-disorder
#10
Xiao-Juan Zhao, Yan-Zi Yang, Yan-Jing Zheng, Shan-Chun Wang, Hong-Mei Gu, Ying Pan, Shui-Juan Wang, Hong-Jiang Xu, Ling-Dong Kong
Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels...
May 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28525945/the-protective-effect-of-luteolin-on-myocardial-ischemia-reperfusion-i-r-injury-through-tlr4-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-pathway
#11
Xu Zhang, Qianming Du, Yan Yang, Jianing Wang, Shuai Dou, Chao Liu, Junguo Duan
The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30min of left anterior descending (LAD) occlusion followed by 24h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1)Sham, (2)I/R, (3)I/R+Lut(40mg/kg), (4)I/R+Lut(80mg/kg) and (5)I/R+Lut(160mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1)control, (2)hypoxia-reoxygenation(H/R), (3)H/R+Lut(5μM), (4)H/R+Lut(10μM) and (5)H/R+Lut(20μM)...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28523794/mineralocorticoid-receptor-associates-with-pro-inflammatory-bias-in-hippocampus-of-spontaneously-hypertensive-rats
#12
María Elvira Brocca, Luciana Pietranera, Maria Meyer, Analia Lima, Paulina Roig, E Ronald de Kloet, Alejandro F De Nicola
Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry...
May 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28523573/activation-of-nlrp3-inflammasome-in-inflammatory-bowel-disease-differences-between-crohn-s-disease-and-ulcerative-colitis
#13
Lazaros-Dimitrios Lazaridis, Aikaterini Pistiki, Evangelos J Giamarellos-Bourboulis, Marianna Georgitsi, Georgia Damoraki, Dimitrios Polymeros, George D Dimitriadis, Konstantinos Triantafyllou
BACKGROUND: NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β. AIMS: To investigate NLRP3 inflammasome activation in inflammatory bowel disease. METHODS: Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28516117/reconstruction-of-the-mouse-inflammasome-system-in-hek293t-cells
#14
Hexin Shi, Anne Murray, Bruce Beutler
The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and the protein kinase NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et al., 2016). When cells are exposed to microbes and/or danger signals, the inflammasome assembles and serves as a platform for the activation of caspase-1. Caspase-1 activation promotes the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and IL-33 as well as pyroptosis induction (Gross et al...
November 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28516116/asc-particle-induced-peritonitis
#15
Lucia de Almeida, Andrea Dorfleutner, Christian Stehlik
In response to pathogen infection and tissue damage, inflammasome sensors such as NLRP3 and AIM2 are activated, which triggers PYRIN domain (PYD)-mediated ASC nucleation, followed by self-perpetuating ASC polymerization, which ultimately culminates in caspase-1 activation, interleukin (IL)-1β and IL-18 processing and release and pyroptosis (Ratsimandresy et al., 2013; Cai et al., 2014). Inflammasomes release not only cytokines, but also the polymeric ASC danger particles (pASC) by pyroptosis, which perpetuate and propagate inflammasome responses to bystander cells to engage cell intrinsic ASC and caspase-1 (Baroja-Mazo et al...
October 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515391/advanced-glycation-end-products-regulate-interleukin-1%C3%AE-production-in-human-placenta
#16
Kotomi Seno, Saoko Sase, Ayae Ozeki, Hironori Takahashi, Akihide Ohkuchi, Hirotada Suzuki, Shigeki Matsubara, Hisataka Iwata, Takehito Kuwayama, Koumei Shirasuna
Maternal obesity is a major risk factor for pregnancy complications, causing inflammatory cytokine release in the placenta, including interleukin-1β (IL-1β), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic and placental inflammation with elevated circulating advanced glycation end products (AGEs). IL-1β is a pivotal inflammatory cytokine associated with obesity and pregnancy complications, and its production is regulated by NLR family pyrin domain-containing 3 (NLRP3) inflammasomes...
May 18, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28508104/quercetin-inhibits-gout-arthritis-in-mice-induction-of-an-opioid-dependent-regulation-of-inflammasome
#17
Kenji W Ruiz-Miyazawa, Larissa Staurengo-Ferrari, Sandra S Mizokami, Talita P Domiciano, Fabiana T M C Vicentini, Doumit Camilios-Neto, Wander R Pavanelli, Phileno Pinge-Filho, Flávio A Amaral, Mauro M Teixeira, Rubia Casagrande, Waldiceu A Verri
We investigated the anti-inflammatory and analgesic effects of quercetin in monosodium urate crystals (MSU)-induced gout arthritis, and the sensitivity of quercetin effects to naloxone, an opioid receptor antagonist. Mice were treated with quercetin, and mechanical hyperalgesia was assessed at 1-24 h after MSU injection. In vivo, leukocyte recruitment, cytokine levels, oxidative stress, NFκB activation, and gp91(phox) and inflammasome components (NLRP3, ASC, Pro-caspase-1, and Pro-IL-1β) mRNA expression by qPCR were determined in the knee joints at 24 h after MSU injection...
May 15, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28507328/pro-inflammatory-ca-activated-k-channels-are-inhibited-by-hydroxychloroquine
#18
María Eugenia Schroeder, Sofía Russo, Carlos Costa, Juliana Hori, Inés Tiscornia, Mariela Bollati-Fogolín, Darío S Zamboni, Gonzalo Ferreira, Ernesto Cairoli, Marcelo Hill
Antimalarials have demonstrated beneficial effects in Systemic Lupus Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ) is a known ion channel inhibitor, this property has not been linked to its anti-inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca(++)-activated K(+) conductance in THP-1 macrophages in a dose-dependent manner...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507179/elevated-expression-of-the-nlrp3-inflammasome-and-its-correlation-with-disease-activity-in-adult-onset-still-disease
#19
Chia-Wei Hsieh, Yi-Ming Chen, Chi-Chen Lin, Kuo-Tung Tang, Hsin-Hua Chen, Wei-Ting Hung, Kuo-Lung Lai, Der-Yuan Chen
OBJECTIVE: The dysregulation of the NLRP3 (NLR containing a pyrin domain) inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease (AOSD) is regarded as an autoinflammatory disease. However, the pathogenic involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in AOSD are currently unknown. METHODS: The mRNA expression of NLRP3 inflammasome signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD and 14 healthy subjects was determined using quantitative-PCR (qPCR)...
May 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28504245/macrophage-derived-il-1%C3%AE-promotes-sterile-inflammation-in-a-mouse-model-of-acetaminophen-hepatotoxicity
#20
Chao Zhang, Jin Feng, Jun Du, Zhiyong Zhuo, Shuo Yang, Weihong Zhang, Weihong Wang, Shengyuan Zhang, Yoichiro Iwakura, Guangxun Meng, Yang-Xin Fu, Baidong Hou, Hong Tang
The metabolic intermediate of acetaminophen (APAP) can cause severe hepatocyte necrosis, which triggers aberrant immune activation of liver non-parenchymal cells (NPC). Overzealous hepatic inflammation determines the morbidity and mortality of APAP-induced liver injury (AILI). Interleukin-1 receptor (IL-1R) signaling has been shown to play a critical role in various inflammatory conditions, but its precise role and underlying mechanism in AILI remain debatable. Herein, we show that NLRP3 inflammasome activation of IL-1β is dispensable to AILI, whereas IL-1α, the other ligand of IL-1R1, accounts for hepatic injury by a lethal dose of APAP...
May 15, 2017: Cellular & Molecular Immunology
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