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Inflammasome

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https://www.readbyqxmd.com/read/29348630/expression-of-inflammasome-proteins-and-inflammasome-activation-occurs-in-human-but-not-in-murine-keratinocytes
#1
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
#2
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
#3
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
#4
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/29343442/the-transcription-factor-stat6-mediates-direct-repression-of-inflammatory-enhancers-and-limits-activation-of-alternatively-polarized-macrophages
#5
Zsolt Czimmerer, Bence Daniel, Attila Horvath, Dominik Rückerl, Gergely Nagy, Mate Kiss, Matthew Peloquin, Marietta M Budai, Ixchelt Cuaranta-Monroy, Zoltan Simandi, Laszlo Steiner, Bela Nagy, Szilard Poliska, Csaba Banko, Zsolt Bacso, Ira G Schulman, Sascha Sauer, Jean-Francois Deleuze, Judith E Allen, Szilvia Benko, Laszlo Nagy
The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29343269/microglial-activation-mediates-chronic-mild-stress-induced-depressive-and-anxiety-like-behavior-in-adult-rats
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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/29338910/synthesis-of-deuterium-labelled-analogues-of-nlrp3-inflammasome-inhibitor-mcc950
#13
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
#14
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
#15
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/29336252/colchicine-in-gout-an-update
#16
Tristan Pascart, Pascal Richette
Despite the fact that colchicine is by far the most ancient treatment for gout, new data are still being gathered. In gout, colchicine's ability to block polymerization of tubulin prevents the activation of the inflammasome. Efficacy of colchicine for the treatment of gout flares has been demonstrated only recently by a randomized-controlled trial, but it still has not been compared to other drugs. Use of colchicine is impaired by the impact of underlying comorbid conditions and drug interactions that can considerably modify its pharmacokinetics and pharmacodynamics...
January 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29334279/uric-acid-and-the-vaccine-adjuvant-activity-of-aluminum-oxy-hydroxide-nanoparticles
#17
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
#18
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
https://www.readbyqxmd.com/read/29329580/evidence-for-the-activation-of-pyroptotic-and-apoptotic-pathways-in-rpe-cells-associated-with-nlrp3-inflammasome-in-the-rodent-eye
#19
Jiangyuan Gao, Jing Z Cui, Eleanor To, Sijia Cao, Joanne A Matsubara
BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved. The prevailing theories consider that each cell death pathway works independently and without regulation of each other. Building upon our previous work in which we induced a short burst of inflammasome activity in vivo, we now investigate the effects of prolonged inflammasome activity on RPE cell death mechanisms in rats...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29328911/western-diet-triggers-nlrp3-dependent-innate-immune-reprogramming
#20
Anette Christ, Patrick Günther, Mario A R Lauterbach, Peter Duewell, Debjani Biswas, Karin Pelka, Claus J Scholz, Marije Oosting, Kristian Haendler, Kevin Baßler, Kathrin Klee, Jonas Schulte-Schrepping, Thomas Ulas, Simone J C F M Moorlag, Vinod Kumar, Min Hi Park, Leo A B Joosten, Laszlo A Groh, Niels P Riksen, Terje Espevik, Andreas Schlitzer, Yang Li, Michael L Fitzgerald, Mihai G Netea, Joachim L Schultze, Eicke Latz
Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity," causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undetectable in serum soon after mice were shifted back to a chow diet (CD). In contrast, myeloid cell responses toward innate stimuli remained broadly augmented...
January 11, 2018: Cell
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