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https://www.readbyqxmd.com/read/29352570/the-nlrp3-inflammasome-and-the-emerging-role-of-colchicine-to-inhibit-atherosclerosis-associated-inflammation
#1
REVIEW
Gonzalo J Martínez, David S Celermajer, Sanjay Patel
Atherosclerosis is considered a chronic inflammatory disease of the arterial wall. Recently, compelling evidence has arisen for the role of monocytes and neutrophils and a particular protein complex that resides within these cells - the NLRP3 inflammasome - in atherosclerosis-associated inflammation. It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability...
December 25, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29352517/mirna-binding-site-variants-of-type-2-diabetes-candidate-loci-predispose-to-gestational-diabetes-mellitus-in-chinese-han-women
#2
Xiaojing Wang, Wei Li, Liangkun Ma, Fan Ping, Juntao Liu, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
AIMS/INTRODUCTION: Emerging evidence suggested that the genetic background of GDM was analogous to T2DM. In contrast to T2DM, the genetic studies for GDM were limited. Accordingly, the aim of this study was to extensively explore the influence of miR-binding-SNPs in T2DM candidate loci on GDM susceptibility in Chinese. METERIALS AND METHODS: A total of 839 GDM and 900 controls were enrolled. Six miR-binding-SNPs were selected from 30 T2DM susceptibility loci and genotyped using TaqMan allelic discrimination assays...
January 20, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29352265/type-i-ifn-operates-pyroptosis-and-necroptosis-during-multidrug-resistant-a-baumannii-infection
#3
Yang Li, Xiaomin Guo, Chunmiao Hu, Yan Du, Chuansheng Guo, Di Wang, Weiheng Zhao, Gonghua Huang, Chunliang Li, Qiumin Lu, Ren Lai, Tao Xu, Xiaopeng Qi
Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumannii is a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29348630/expression-of-inflammasome-proteins-and-inflammasome-activation-occurs-in-human-but-not-in-murine-keratinocytes
#4
Jennifer Sand, Eric Haertel, Thomas Biedermann, Emmanuel Contassot, Ernst Reichmann, Lars E French, Sabine Werner, Hans-Dietmar Beer
Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as macrophages or dendritic cells, express and activate inflammasomes. However, it has also been demonstrated that human primary keratinocytes activate different types of inflammasomes in vitro, for example, upon UVB irradiation or viral infection...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29347884/differential-mrna-expression-of-inflammasome-genes-nlrp1-and-nlrp3-in-abdominal-aneurysmal-and-occlusive-aortic-disease
#5
Carmen Gonzalez-Hidalgo, Joaquin De Haro, Silvia Bleda, Cristina Cañibano, Ignacio Michel, Francisco Acin
NLRP1 and NLRP3 inflammasomes might differentially mediate the chronic inflammatory response in abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD). We measure differential relative gene expression of NLRP1 and NLRP3 inflammasomes in aortic tissues from 30 patients undergoing AAA open repair compared to aortic biopsies from 30 patients undergoing surgery to treat AOD. Aortic wall samples from autopsy without aortic disease were used as controls. NLRP3 was overexpressed in patients with AAA and AOD (RQ 1...
January 1, 2018: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/29345311/calcium-sensing-receptor-activates-the-nlrp3-inflammasome-in-ls14-preadipocytes-mediated-by-erk1-2-signaling
#6
Amanda D'Espessailles, Yuly A Mora, Cecilia Fuentes, Mariana Cifuentes
The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding and preventing the cardiometabolic consequences of obesity. We have proposed a model where activation of the G protein-coupled calcium sensing receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon activation, CaSR can mediate the expression and secretion of proinflammatory factors in human preadipocytes, adipocytes and adipose tissue explants. One possible pathway involved in CaSR-induced inflammation is the activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes maturation and secretion of interleukin (IL)-1β...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29344132/aberrant-nlrp3-inflammasome-associated-with-aryl-hydrocarbon-receptor-potentially-contributes-to-the-imbalance-of-t-helper-cells-in-patients-with-acute-myeloid-leukemia
#7
Yan Jia, Chen Zhang, Mingqiang Hua, Min Wang, Ping Chen, Daoxin Ma
Acute myeloid leukemia (AML) is a hematological malignancy in which the immune response serves a pivotal role in progression. Aryl hydrocarbon receptor (AHR) is involved in the modulation of the immune system, particularly in the differentiation of T-helper cell (Th) subsets. Although the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated as essential in the pathogenesis of autoimmune and inflammatory diseases, the role it serves in the development of AML remains unknown. Therefore, in order to identify and describe the possible roles of AHR, as well as NLRP3 inflammasome, in the pathogenesis of AML and their relationship with Th subsets (Th1 Th22), the present study investigated the mRNA expression levels of AHR and NLRP3 inflammasome molecules in the peripheral blood and bone marrow...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343269/microglial-activation-mediates-chronic-mild-stress-induced-depressive-and-anxiety-like-behavior-in-adult-rats
#8
Ya-Lin Wang, Qiu-Qin Han, Wen-Qing Gong, Dong-Hui Pan, Li-Zheng Wang, Wei Hu, Min Yang, Bing Li, Jin Yu, Qiong Liu
BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. METHODS: We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS)...
January 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29342502/antiphospholipid-antibodies-inhibit-trophoblast-toll-like-receptor-and-inflammasome-negative-regulators
#9
Melissa J Mulla, Ingrid C Weel, Julie A Potter, Stefan M Gysler, Jane E Salmon, Maria T S Peraçoli, Carla V Rothlin, Lawrence W Chamley, Vikki M Abrahams
OBJECTIVE: Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications associated with poor placentation and placental inflammation. While these antibodies are heterogeneous, some anti-β2 GPI antibodies can activate human first trimester trophoblast TLR4 and NLRP3. The objective of this study was to determine the role of negative regulators of TLR and inflammasome function in aPL-induced trophoblast inflammation. METHODS: Human trophoblast cells were treated with or without anti-β2 GPI aPL or control IgG in the presence or absence of the common TAM receptor ligand, GAS6, or the autophagy inducer, rapamycin...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342053/gradual-symmetric-progression-of-dfna34-hearing-loss-caused-by-an-nlrp3-mutation-and-cochlear-autoinflammation
#10
Hiroshi Nakanishi, Yoshiyuki Kawashima, Kiyoto Kurima, Julie A Muskett, H Jeffrey Kim, Carmen C Brewer, Andrew J Griffith
OBJECTIVE: To characterize the audiometric phenotype of autosomal-dominant DFNA34 hearing loss (HL) caused by a missense substitution in the NLRP3 gene. NLRP3 encodes a critical component of the NLRP3 inflammasome that is activated in innate immune responses. STUDY DESIGN: This study was conducted under protocol 01-DC-0229 approved by the NIH Combined Neurosciences IRB. We performed medical and developmental history interviews and physical and audiological examinations of affected individuals with DFNA34 HL caused by the p...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29340626/suppression-of-nlrp3-inflammasome-by-oral-treatment-with-sulforaphane-alleviates-acute-gouty-inflammation
#11
Gabsik Yang, Sang Hyeon Yeon, Hye Eun Lee, Han Chang Kang, Yong Yeon Cho, Hye Suk Lee, Joo Young Lee
Objective: The aetiology of gout is closely linked to the deposition of monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we investigated whether oral administration of an NLRP3 inhibitor would be effective to attenuate the symptoms of gout. Methods: The effects of oral administration with sulforaphane (SFN) were examined in two mouse models of acute gout induced by injection of MSU crystals into footpads or air pouch...
January 10, 2018: Rheumatology
https://www.readbyqxmd.com/read/29339754/baicalin-modulates-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-signaling-in-porcine-aortic-vascular-endothelial-cells-infected-by-haemophilus-parasuis-causing-gl%C3%A3-sser-s-disease
#12
Shulin Fu, Huashan Liu, Lei Xu, Yinsheng Qiu, Yu Liu, Zhongyuan Wu, Chun Ye, Yongqing Hou, Chien-An Andy Hu
Haemophilus parasuis (H. parasuis) can cause vascular inflammatory injury, but the molecular basis of this effect remains unclear. In this study,we investigated the effect of the anti-inflammatory, anti-microbial and anti-oxidant agent, baicalin, on the nuclear factor (NF)-κB and NLRP3 inflammasome signaling pathway in pig primary aortic vascular endothelial cells. Activation of the NF-κB and NLRP3 inflammasome signaling pathway was induced in H. parasuis-infected cells. However, baicalin reduced the production of reactive oxygen species, apoptosis, and activation of the NF-κB and NLRP3 inflammasome signaling pathway in infected cells...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339744/human-caspase-4-detects-tetra-acylated-lps-and-cytosolic-francisella-and-functions-differently-from-murine-caspase-11
#13
Brice Lagrange, Sacha Benaoudia, Pierre Wallet, Flora Magnotti, Angelina Provost, Fanny Michal, Amandine Martin, Flaviana Di Lorenzo, Bénédicte F Py, Antonio Molinaro, Thomas Henry
Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339210/the-nlrp3-inflammasome-role-in-metabolic-disorders-and-regulation-by-metabolic-pathways
#14
Danlu Jiang, Sheng Chen, Ruyu Sun, Xue Zhang, Di Wang
Inflammasomes are large multimolecular complexes present in the cytosol of stimulated immune cells; they mediate the activation of caspase-1, leading to cellular pyroptosis. So far, a variety of studies on inflammasomes have emerged, and the best-studied is the NLRP3 inflammasome that is involved in many inflammatory responses. Furthermore, its relationship with metabolism is gaining increasing attention in this field. In this review, we discuss the importance of the NLRP3 inflammasome in metabolic disorders and its close association with metabolic pathways...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#15
Cui-Cui Liu, Zhu-Xi Huang, Xiao Li, Kai-Feng Shen, Meng Liu, Han-Dong Ouyang, Su-Bo Zhang, Yu-Ting Ruan, Xiao-Long Zhang, Shao-Ling Wu, Wen-Jun Xin, Chao Ma
Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29338910/synthesis-of-deuterium-labelled-analogues-of-nlrp3-inflammasome-inhibitor-mcc950
#16
Manohar Salla, Mark S Butler, Nicholas L Massey, Janet C Reid, Matthew A Cooper, Avril A B Robertson
This study describes the syntheses of di, tetra and hexa deuterated analogues of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were incorporated into the 1,2,3,5,6,7-hexahydro-s-indacene moiety, whereas in the hexa deuterated MCC950 deuteriums were incorporated into the 2-(furan-3-yl)propan-2-ol moiety. The di deuterated MCC950 analogue was synthesised from 4-amino-3,5,6,7-tetrahydro-s-indacen-1(2H)-one 5. Tetra deuterated analogues were synthesised in 10 chemical steps starting with 5-bromo-2,3-dihydro-1H-inden-1-one 9, whereas the hexa deuterated analogue was synthesised in four chemical steps starting with ethyl-3-furoate 24...
December 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29338075/lkb1-ampk-mediated-regulation-by-gentiopicroside-ameliorates-p2x7r-dependent-alcoholic-hepatosteatosis
#17
Xia Li, Yu Zhang, Quan Jin, Kai-Li Xia, Min Jiang, Ben-Wen Cui, Yan-Ling Wu, Shun-Zong Song, Li-Hua Lian, Ji-Xing Nan
BACKGROUND AND PURPOSE: Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis. We investigated whether this process would be modulated by gentiopicroside (GPS), which is the main active secoiridoid glycoside from Gentiana manshurica Kitagawa. EXPERIMENTAL APPROACH: In vivo models of acute and chronic alcoholic hepatosteatosis were established by intragastrically administrated ethanol or using chronic plus binge ethanol feeding of Lieber-DeCarli liquid diet to male C57BL/6 mice...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29336982/il-6-receptor-blockade-ameliorates-diabetic-nephropathy-via-inhibiting-inflammasome-in-mice
#18
Rui Wu, Xuanchen Liu, Jianyong Yin, Huijuan Wu, Xiulei Cai, Niansong Wang, Youcun Qian, Feng Wang
BACKGROUND AND OBJECTIVE: Interleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus. METHODS: Twelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed...
January 11, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29334279/uric-acid-and-the-vaccine-adjuvant-activity-of-aluminum-oxy-hydroxide-nanoparticles
#19
Sachin G Thakkar, Haiyue Xu, Xu Li, Zhengrong Cui
In an effort to improve the adjuvanticity of insoluble aluminum salts, we discovered that the adjuvant activity of aluminum salt nanoparticles is significantly stronger than aluminum salt microparticles, likely related to nanoparticle's stronger ability to directly activate NLRP3 inflammasome as the nanoparticles are more efficiently taken up by phagocytic cells. Endogenous signals such as uric acid from cell damage or death caused by the cytotoxicity of aluminum salts are thought to indirectly activate inflammasome, prompting us to hypothesize that the potent adjuvant activity of aluminum salt nanoparticles is also related to their ability to stimulate uric acid production...
January 15, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29331080/design-synthesis-and-evaluation-of-novel-oxazaborine-inhibitors-of-the-nlrp3-inflammasome
#20
Alex George Baldwin, Victor S Tapia, Tessa Swanton, Claire S White, James A Beswick, David Brough, Sally Freeman
The NLRP3 inflammasome is an important regulator of the sterile inflammatory response and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL 1β)/IL-18, and pyroptotic cell death. Inappropriate activation of NLRP3 drives a chronic inflammatory response and is implicated in several non-communicable diseases, including gout, atherosclerosis, type II diabetes and Alzheimer's disease. In this study, we report the design, synthesis and biological evaluation of novel boron compounds (NBCs) as NLRP3 inflammasome inhibitors...
January 13, 2018: ChemMedChem
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