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https://www.readbyqxmd.com/read/28726778/protection-of-mcc950-against-high-glucose-induced-human-retinal-endothelial-cell-dysfunction
#1
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
#2
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/28726636/live-cell-visualization-of-gasdermin-d-driven-pyroptotic-cell-death
#3
Joseph K Rathkey, Bryan L Benson, Steven M Chirieleison, Jie Yang, Tsan S Xiao, George R Dubyak, Alex Y Huang, Derek W Abbott
Pyroptosis is a form of cell death important in defenses against pathogens, but which can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, gasdermin D (GSDMD), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724943/aim2-inflammasome-mediated-pyroptosis-in-enterovirus-a71-infected-neuronal-cells-restricts-viral-replication
#4
Thinesshwary Yogarajah, Kien Chai Ong, David Perera, Kum Thong Wong
Encephalomyelitis is a well-known complication of hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71) infection. Viral RNA/antigens could be detected in the central nervous system (CNS) neurons in fatal encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in melanoma 2 (AIM2) inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and protein expression in EV-A71-infected SK-N-SH cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#5
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#6
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/28722725/the-monogenic-autoinflammatory-diseases-define-new-pathways-in-human-innate-immunity-and-inflammation
#7
REVIEW
Kalpana Manthiram, Qing Zhou, Ivona Aksentijevich, Daniel L Kastner
Autoinflammatory diseases were first recognized nearly 20 years ago as distinct clinical and immunological entities caused by dysregulation in the innate immune system. Since then, advances in genomic techniques have led to the identification of new monogenic disorders and their corresponding signaling pathways. Here we review these monogenic autoinflammatory diseases, ranging from periodic fever syndromes caused by dysregulated inflammasome-mediated production of the cytokine IL-1β to disorders arising from perturbations in signaling by the transcription factor NF-κB, ubiquitination, cytokine signaling, protein folding, type I interferon production and complement activation, and we further examine their molecular mechanisms...
July 19, 2017: Nature Immunology
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/28720729/inhibition-of-inflammasome-dependent-interleukin-1%C3%AE-production-by-streptococcal-nad-glycohydrolase-evidence-for-extracellular-activity
#9
Dóra Hancz, Elsa Westerlund, Benedicte Bastiat-Sempe, Onkar Sharma, Christine Valfridsson, Lena Meyer, John F Love, Maghnus O'Seaghdha, Michael R Wessels, Jenny J Persson
Group A Streptococcus (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD(+)-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease. NADase can be translocated into host cells by a SLO-dependent mechanism, and cytosolic NADase has been assigned multiple properties such as protection of intracellularly located GAS bacteria and induction of host cell death through energy depletion...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28716882/protein-kinase-d-at-the-golgi-controls-nlrp3-inflammasome-activation
#10
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
#11
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
#12
(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
#13
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
#14
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
#15
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/28704412/synthetic-preimplantation-factor-pif-prevents-fetal-loss-by-modulating-lps-induced-inflammatory-response
#16
Nicoletta Di Simone, Fiorella Di Nicuolo, Riccardo Marana, Roberta Castellani, Francesco Ria, Manuela Veglia, Giovanni Scambia, Daniel Surbek, Eytan Barnea, Martin Mueller
Maternal control of inflammation is essential during pregnancy and an exaggerated response is one of the underlying causes of fetal loss. Inflammatory response is mediated by multiple factors and Toll-like receptors (TLRs) are central. Activation of TLRs results in NALP-3 mediated assembly of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 into the inflammasome and production of pro-inflammatory cytokines IL-1β and IL-18. Given that preventing measures are lacking, we investigated PreImplantation Factor (PIF) as therapeutic option as PIF modulates Inflammation in pregnancy...
2017: PloS One
https://www.readbyqxmd.com/read/28701727/free-immunoglobulin-light-chain-flc-promotes-murine-colitis-and-colitis-associated-colon-carcinogenesis-by-activating-the-inflammasome
#17
Junfan Ma, Dongyang Jiang, Xiaoting Gong, Wenwei Shao, Zhu Zhu, Weiyan Xu, Xiaoyan Qiu
Numerous studies have demonstrated that free Ig light chain (FLC), a novel inflammation mediator, participates in many inflammatory diseases by activating mast cells and extending the survival of neutrophils. However, it remains unclear whether FLC is involved in colitis and colitis-associated colon carcinogenesis (CAC). In this study, we found a significant increase in FLC in murine models of DSS (Dextran Sulfate Sodium Salt)-induced colitis and CAC compared to controls. Peptide F991, a functional blocker of FLC, significantly attenuated colitis progression, which included abrogating the development of diarrhea and tumor burden, elevating survival rate, greatly reducing the infiltration of inflammatory cells (such as ROS(+) active neutrophils), especially reducing tumorigenesis in CAC...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701426/dynamics-of-in-vivo-asc-speck-formation
#18
Paola Kuri, Nicole L Schieber, Thomas Thumberger, Joachim Wittbrodt, Yannick Schwab, Maria Leptin
Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into specks, large signaling platforms considered hallmarks of inflammasome activation. Because a lack of in vivo tools has prevented the study of endogenous ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus triggered speck formation and rapid pyroptosis in keratinocytes in vivo...
July 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28700567/recombinant-ccn1-prevents-hyperoxia-induced-lung-injury-in-neonatal-rats
#19
Ruben Vaidya, Ronald Zambrano, Julia K Hummler, Shihua Luo, Matthew R Duncan, Karen Young, Lester F Lau, Shu Wu
BACKGROUND: Cystein rich protein 61 (Cyr61/CCN1) is a member of the CCN family of matricellular proteins that plays an improtant role in tissue development and remodeling. However, the role of CCN1 in in the pathogensis of bronchopulmonary dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1 on a hyperoxia-induced lung injury model in neonatal rats. METHODS: In experiment 1: newborn rats were randomized to room air (RA) or 85% oxygen (O2) for 7 or 14 days and we assessed the expression of CCN1...
July 12, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28698859/inflammasome-as-a-therapeutic-target-for-cancer-prevention-and-treatment
#20
REVIEW
Huyen Trang Ha Thi, Suntaek Hong
Chronic inflammation is a critical modulator of carcinogenesis through secretion of inflammatory cytokines, which leads to the formation of an inflammatory microenvironment. In this process, the inflammasome plays an important role in the expression and activation of interleukin (IL)-1β and IL-18 to promote cancer development. The inflammasome is a multiprotein complex consisting of several nucleotide-binding domain and leucine-rich repeat containing receptor, adaptor proteins, and caspase 1 (CASP1). It senses the various intracellular (damage-associated molecular patterns) and extracellular (pathogen-associated molecular patterns) stimuli...
June 2017: Journal of Cancer Prevention
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