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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/28714351/activation-of-nlrp3-inflammasome-in-peripheral-nerve-contributes-to-paclitaxel-induced-neuropathic-pain
#5
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/28712913/acute-ochratoxin-a-exposure-induces-inflammation-and-apoptosis-in-human-embryonic-kidney-hek293-cells
#6
Shanel Raghubeer, Savania Nagiah, Anil A Chuturgoon
Ochratoxin A (OTA), a common contaminant of grain and fruit and known carcinogen, has been linked to impaired antioxidant response and cellular repair. The effect of OTA on inflammation in cells has not been explored. This study investigated OTA's influence on inflammatory mediators using a range of OTA concentrations (0.5 μM (sub-IC50), 1.2 μm (IC50) and 2 μm (supra-IC50)) on human embryonic kidney (HEK293) cells over 24hr. The markers of inflammation in HEK293 cells were evaluated using the following techniques: western blotting (phosphorylated (p-)NFκB (Ser536), p-IKK (Ser176/180) and p-p53 (Ser392), total NFκB, IKK, IκBα and p53), luminometry (caspases 1, 3/7, 8, 9, ATP) and ELISA to determine IL-1β levels...
July 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28712670/production-and-regulation-of-interleukin-1-family-cytokines-at-the-materno-fetal-interface
#7
Louis M Scott, Aled H Bryant, April Rees, Billy Down, Ruth H Jones, Catherine A Thornton
IL-1 family members regulate innate immune responses, are produced by gestation-associated tissues, and have a role in healthy and adverse pregnancy outcomes. To better understand their role at the materno-fetal interface we used a human tissue explant model to map lipopolysaccharide (LPS)-stimulated production of IL-1α, IL-1β, IL-18, IL-33, IL-1Ra, IL-18BPa, ST2 and IL-1RAcP by placenta, choriodecidua and amnion. Caspase-dependent processing of IL-1α, IL-1β, IL-18, and IL-33 and the ability of IL-1α, IL-1β, IL-18, and IL-33 to regulate the production of IL-1RA, IL-18BPa, ST2 and IL-1RAcP was also determined...
July 13, 2017: Cytokine
https://www.readbyqxmd.com/read/28711657/kaempferol-impedes-il-32-induced-monocyte-macrophage-differentiation
#8
Sun-Young Nam, Hyun-Ja Jeong, Hyung-Min Kim
Kaempferol possesses a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and anticancer properties. The present study sought to evaluate the effects and possible pharmacological mechanisms of kaempferol on interleukin (IL)-32-induced monocyte-macrophage differentiation. In this study, we performed flow cytometry assay, immunocytochemical staining, quantitative real-time PCR, enzyme-linked immuno sorbent assay, caspase-1 assay, and Western blotting to observe the effects and underlying mechanisms of kaempferol using the human monocyte cell line THP-1...
July 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28709622/genipin-protects-d-galactosamine-and-lipopolysaccharide-induced-hepatic-injury-through-suppression-of-the-necroptosis-mediated-inflammasome-signaling
#9
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
#10
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
#11
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
#12
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/28698859/inflammasome-as-a-therapeutic-target-for-cancer-prevention-and-treatment
#13
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
https://www.readbyqxmd.com/read/28694089/the-potential-protective-role-of-taurine-against-experimental-allergic-inflammation
#14
Sun-Young Nam, Hyung-Min Kim, Hyun-Ja Jeong
AIMS: Taurine has been widely evaluated as a potential therapeutic agent in chronic inflammatory disorders and various infections. However, the potential role of taurine in regulating allergic inflammatory responses is currently unknown. MATERIALS AND METHODS: The present study was designed to evaluate the in vitro effects of taurine on the levels of thymic stromal lymphopoietin (TSLP) and other pro-inflammatory cytokines and activation of caspase-1 and nuclear factor (NF)-κB as well as the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-triggered human mast cell line, HMC-1 cells...
July 7, 2017: Life Sciences
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/28691428/stat-proteins-as-intracellular-regulators-of-resistance-to-myocardial-injury-in-context-of-cardiac-remodeling-and-targeting-for-therapy
#16
REVIEW
Andrzej Wincewicz, Stanislaw Sulkowski
Roles of STAT (signal transducers and activators of transcription) proteins are widely discussed in relation to other agents like IFN-γ that are involved in cardiovascular diseases. STAT3 protects cardiomyocytes during endotoxic shock and ischemia and prolongs survival of these cells by activation of antiapoptotic genes like bcl-2 and c-fos. Moreover, IL-6 dependent expression of STAT3 probably is responsible for hypertrophy of cardiomyocytes. On the contrary STAT1 mediates cell death by induction of caspase-1...
June 27, 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28686578/culling-of-apcs-by-inflammatory-cell-death-pathways-restricts-tim3-and-pd-1-expression-and-promotes-the-survival-of-primed-cd8-t-cells
#17
Rajen Patel, Kwangsin Kim, Bojan Shutinoski, Kristina Wachholz, Lakshmi Krishnan, Subash Sad
We evaluated the impact of premature cell death of antigen-presenting cells (APCs) by Caspase-1- and RipK3-signaling pathways on CD8(+) T-cell priming during infection of mice with Salmonella typhimurium (ST). Our results indicate that Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not influence the initial activation of CD8(+) T cells. However, the maintenance of primed CD8(+) T cells was greatly compromised when both these pathways were disabled. Caspase-1- and RipK3-signaling did not influence NF-κB signaling in APCs, but synergized to promote processing of IL-1 and IL-18...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28684545/macrolides-protect-against-pseudomonas-aeruginosa-infection-via-inhibition-of-inflammasomes
#18
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/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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