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NLRP3 inflammasome

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https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#1
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28730512/nlrp3-deletion-inhibits-the-non-alcoholic-steatohepatitis-development-and-inflammation-in-kupffer-cells-induced-by-palmitic-acid
#2
Can Cai, Xiwen Zhu, Peizhi Li, Jinzheng Li, Jianping Gong, Wei Shen, Kun He
The cleavage and secretion of pro-inflammatory cytokines IL-1β and IL-18 is regulated by NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome activation. Kupffer cells (KCs) are implicated in the pathogenesis of various liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and liver fibrosis. However, the role of NLRP3 played in the non-alcoholic steatohepatitis (NASH) has yet to be evaluated. In the present study, methionine-choline-deficient (MCD) diet was used to establish the mice NASH model...
July 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28729463/dietary-pufas-attenuate-nlrp3-inflammasome-activation-via-enhancing-macrophage-autophagy
#3
Lulu Shen, Yan Yang, Tiantong Ou, Chia-Chi C Key, Sarah H Tong, Russel C Sequeira, Jonathan M Nelson, Yan Nie, Zhan Wang, Elena Boudyguina, Swapnil V Shewale, Xuewei Zhu
Dietary PUFAs reduce atherosclerosis and macrophage inflammation, but how NLRP3 inflammasome activation and autophagy influence PUFA-mediated atheroprotection is poorly understood. We fed Ldlr-/- mice diets containing 10% (calories) palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% of calories as PO, fish oil (FO), echium oil (EO, containing 18:4 n-3), or borage oil (BO, containing 18:3 n-6). Inflammasome activation, autophagic flux, and mitochondrial function were measured in peritoneal macrophages, blood monocytes, or liver from diet-fed mice...
July 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28729291/stimulator-of-ifn-genes-mediated-dna-sensing-pathway-is-suppressed-by-nlrp3-agonists-and-regulated-by-mitofusin-1-and-tbc1d15-mitochondria-dynamics-mediators
#4
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
July 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28726778/protection-of-mcc950-against-high-glucose-induced-human-retinal-endothelial-cell-dysfunction
#5
Yi Zhang, Xuehua Lv, Zizhong Hu, Xiaojian Ye, Xinhua Zheng, Yuzhi Ding, Ping Xie, Qinghuai Liu
Diabetic retinopathy (DR) is a well-known microvascular complication related to inflammation. Mcc950 is a potent and specific inhibitor of the NLRP3 inflammasome but its influence on DR has not been studied. Thus, we evaluated the anti-inflammatory effects of Mcc950 on high-glucose-induced human retinal endothelial cells (HRECs) and the potential underlying mechanism. In surgical excised proliferative membranes from DR patients, high expression of NLRP3, caspase 1 and IL-1β was observed and co-localization of NLRP3 and IL-1β occurred in CD31+ labeled HRECs...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726774/interleukin-22-ameliorated-renal-injury-and-fibrosis-in-diabetic-nephropathy-through-inhibition-of-nlrp3-inflammasome-activation
#6
Shaofei Wang, Yubin Li, Jiajun Fan, Xuyao Zhang, Jingyun Luan, Qi Bian, Tao Ding, Yichen Wang, Ziyu Wang, Ping Song, Daxiang Cui, Xiaobin Mei, Dianwen Ju
Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with metabolic disorders and chronic inflammation. Although the cytokine IL-22 was initially implicated in the pathogenesis of chronic inflammatory diseases, recent studies suggested that IL-22 could suppress inflammatory responses and alleviate tissue injury. Herein, we examined the role of IL-22 in DN. We found that serum levels of IL-22 were significantly downregulated in both patients and mice with DN. The expression of IL-22 was further decreased with the progression of DN, whereas IL-22 gene therapy significantly ameliorated renal injury and mesangial matrix expansion in mice with established nephropathy...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#7
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722711/limiting-inflammation-the-negative-regulation-of-nf-%C3%AE%C2%BAb-and-the-nlrp3-inflammasome
#8
REVIEW
Inna S Afonina, Zhenyu Zhong, Michael Karin, Rudi Beyaert
A properly mounted immune response is indispensable for recognizing and eliminating danger arising from foreign invaders and tissue trauma. However, the 'inflammatory fire' kindled by the host response must be tightly controlled to prevent it from spreading and causing irreparable damage. Accordingly, acute inflammation is self-limiting and is normally attenuated after elimination of noxious stimuli, restoration of homeostasis and initiation of tissue repair. However, unresolved inflammation may lead to the development of chronic autoimmune and degenerative diseases and cancer...
July 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28716882/protein-kinase-d-at-the-golgi-controls-nlrp3-inflammasome-activation
#9
Zhirong Zhang, Gergö Meszaros, Wan-Ting He, Yanfang Xu, Helena de Fatima Magliarelli, Laurent Mailly, Michael Mihlan, Yansheng Liu, Marta Puig Gámez, Alexander Goginashvili, Adrien Pasquier, Olga Bielska, Bénédicte Neven, Pierre Quartier, Rudolf Aebersold, Thomas F Baumert, Philippe Georgel, Jiahuai Han, Romeo Ricci
The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated by MAM-derived effectors. Here, we show that in response to inflammasome activators, MAMs localize adjacent to Golgi membranes...
July 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28714351/activation-of-nlrp3-inflammasome-in-peripheral-nerve-contributes-to-paclitaxel-induced-neuropathic-pain
#10
Min Jia, Caihua Wu, Fang Gao, Hongchun Xiang, Ning Sun, Ping Peng, Jingjing Li, Xiaocui Yuan, Hongping Li, Xianfang Meng, Bo Tian, Jing Shi, Man Li
Background Paclitaxel is commonly used as a cancer chemotherapy drug that frequently causes peripheral neuropathic pain. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein, and caspase-1, which functions to switch on the inflammatory process and the release of interleukin-1β. Growing evidences have supported that peripheral interleukin-1β is critical in enhancing paclitaxel-induced neuropathic pain. However, whether activation of NLRP3 inflammasome in peripheral nerve contributes to paclitaxel-induced neuropathic pain is still unclear...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28714293/research-highlights
#11
(no author information available yet)
In this issue, we highlight a report from Sack et al. on a mechanism linking fasting to inhibition of NLRP3 inflammasome activation, a study from Brodsky and colleagues on ERAD substrate recognition and Cdc48p-faciliated retrotranslocation, and a study from Shindou et al. on a role for DHA in maintaining disc morphology of retinal photoreceptor cells.
July 2017: FEBS Journal
https://www.readbyqxmd.com/read/28710289/nutritional-modulation-of-metabolic-inflammation
#12
REVIEW
Anna M Kirwan, Yvonne M Lenighan, Marcella E O'Reilly, Fiona C McGillicuddy, Helen M Roche
Metabolic inflammation is a very topical area of research, wherein aberrations in metabolic and inflammatory pathways probably contribute to atherosclerosis, insulin resistance (IR) and type 2 diabetes. Metabolic insults arising from obesity promote inflammation, which in turn impedes insulin signalling and reverse cholesterol transport (RCT). Key cells in the process are metabolically activated macrophages, which up-regulate both pro- and anti-inflammatory pathways in response to lipid spillover from adipocytes...
July 14, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28709622/genipin-protects-d-galactosamine-and-lipopolysaccharide-induced-hepatic-injury-through-suppression-of-the-necroptosis-mediated-inflammasome-signaling
#13
Min-Jong Seo, Jeong-Min Hong, Seok-Joo Kim, Sun-Mee Lee
Acute liver failure (ALF) is a life-threatening syndrome resulting from massive inflammation and hepatocyte death. Necroptosis, a programmed cell death controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, has been shown to play an important role in regulating inflammation via crosstalk between other intracellular signaling. The inflammasome is a major intracellular multiprotein that induces inflammatory responses by mediating immune cell infiltration, thus potentiating injury. Genipin, a major active compound of the gardenia fruit, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties...
July 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28708885/pioglitazone-ameliorates-glomerular-nlrp3-inflammasome-activation-in-apolipoprotein-e-knockout-mice-with-diabetes-mellitus
#14
Yao Wang, Bo Yu, Li Wang, Ming Yang, Zhiyin Xia, Wei Wei, Fengyu Zhang, Xiaochen Yuan
OBJECTIVE: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. METHODS: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO...
2017: PloS One
https://www.readbyqxmd.com/read/28691886/salivary-levels-of-nlrp3-inflammasome-related-proteins-as-potential-biomarkers-of-periodontal-clinical-status
#15
Diana M Isaza-Guzmán, Verónica M Medina-Piedrahíta, Carolina Gutiérrez-Henao, Sergio I Tobón-Arroyave
BACKGROUND: Emerging evidence suggests that the activation of inflammasomes plays a central mechanism in the pathogenesis of periodontitis. This study aimed to compare the salivary levels of nod-like receptor family pyrin domain containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cysteine aspartase-1 (caspase-1), and interleukin-1 beta (IL-1β) from individuals with aggressive (AgP) or chronic periodontitis (CP) and healthy controls (HC), as well as elucidate its association with the periodontal clinical status...
July 10, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28687790/chronic-inflammation-triggered-by-the-nlrp3-inflammasome-in-myeloid-cells-promotes-growth-plate-dysplasia-by-mesenchymal-cells
#16
Chun Wang, Can-Xin Xu, Yael Alippe, Chao Qu, Jianqiu Xiao, Ernestina Schipani, Roberto Civitelli, Yousef Abu-Amer, Gabriel Mbalaviele
Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684545/macrolides-protect-against-pseudomonas-aeruginosa-infection-via-inhibition-of-inflammasomes
#17
Li-Chao Fan, Jie-Lu Lin, Jia-Wei Yang, Bei Mao, Hai-Wen Lu, Bao-Xue Ge, Augustine M K Choi, Jinfu Xu
Background Macrolides antibiotics have been used effectively in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. Methods We established a mouse model of chronic lung infection using P. aeruginosa agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment...
July 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28684277/nlrp3-inflammasome-activation-mediates-fatigue-like-behaviors-in-mice-via-neuroinflammation
#18
Ziteng Zhang, Xiujuan Ma, Zhenna Xia, Jikuai Chen, Yangang Liu, Yongchun Chen, Jiangbo Zhu, Jinfeng Li, Huaiyu Yu, Ying Zong, Guocai Lu
Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions. We employed repeated forced swims to establish a model of CFS in mice. NLRP3 knockout (KO) mice were also used to explore NLRP3 inflammasome activation in the mechanisms of CFS, using the same treatment...
July 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28683365/resveratrol-alleviates-cerebral-ischemia-reperfusion-injury-in-rats-by-inhibiting-nlrp3-inflammasome-activation-through-sirt1-dependent-autophagy-induction
#19
Qi He, Zhenyu Li, Yueting Wang, Yanghao Hou, Lingyu Li, Jing Zhao
Resveratrol has been reported to protect against cerebral ischemia/reperfusion (I/R) injury in rats, but the underlying mechanism is unclear. In the current study, we examined whether resveratrol ameliorates cerebral I/R injury by inhibiting NLRP3 inflammasome-derived inflammation and whether autophagy is involved in this process. In addition, we explored the role of Sirt1 in resveratrol-mediated protective effects. To answer these questions, healthy male Sprague-Dawley rats were exposed to middle cerebral artery occlusion for 1h followed by 24h reperfusion...
July 3, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28683296/inflammasomes-on-the-crossroads-of-innate-immune-recognition-and-metabolic-control
#20
REVIEW
Tomasz Próchnicki, Eicke Latz
Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling...
July 5, 2017: Cell Metabolism
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