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NLRP3 inflammasome

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https://www.readbyqxmd.com/read/29457838/bax-inhibitor-1-protects-from-non-alcoholic-steatohepatitis-by-limiting-ire1%C3%AE-signaling
#1
Cynthia Lebeaupin, Déborah Vallée, Déborah Rousseau, Stéphanie Patouraux, Stéphanie Bonnafous, Gilbert Adam, Frederic Luciano, Carmelo Luci, Rodolphe Anty, Antonio Iannelli, Sandrine Marchetti, Guido Kroemer, Sandra Lacas-Gervais, Albert Tran, Philippe Gual, Béatrice Bailly-Maitre
Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29456821/resveratrol-decreases-apoptosis-and-nlrp3-complex-expressions-in-experimental-varicocele-rat-model
#2
Elnaz Hajipour, Farideh Jalali Mashayekhi, Ghasem Mosayebi, Maryam Baazm, Adib Zendedel
Objectives: Varicocele is an abnormal dilation in the testicular vein, which can cause hypoxia, reactive oxygen species accumulation, elevation in testicular temperature, and promote apoptosis and increase proinflammatory cytokine production. According to the varicocele pathophysiology, it is possible that a group of cytosolic receptors called nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes also involve in varicocele pathogenesis...
February 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29456024/protective-effects-of-flagellin-a-n-c-against-radiation-induced-nlr-pyrin-domain-containing-3-inflammasome-dependent-pyroptosis-in-intestinal-cells
#3
Dongming Wu, Rong Han, Shihua Deng, Teng Liu, Ting Zhang, Hongxiang Xie, Ying Xu
PURPOSE: To investigate changes induced in mouse intestines after irradiation and to explore the potential radioprotective effects of flagellin A N/C (FlaAN/C). METHODS AND MATERIALS: A mouse model of radiation-induced enteropathy was used in this study. A 10-Gy abdominal irradiation was performed on FlaAN/C- and vehicle-injected mice to explore the role of FlaAN/C in intestinal radiation injury and to study the molecular mechanism in this process. In the intestinal tissue, pathologic changes were investigated by hematoxylin and eosin staining, TUNEL staining, and immunohistochemistry; Western blotting and quantitative reverse transcription-polymerase chain reaction were used to determine the changes in protein and messenger RNA levels, respectively; and an enzyme-linked immunosorbent assay was performed to determine protein concentration in serum...
January 31, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29452983/orchestration-of-nlrp3-inflammasome-activation-by-ion-fluxes
#4
REVIEW
Tao Gong, Yanqing Yang, Tengchuan Jin, Wei Jiang, Rongbin Zhou
The assembly of the NLRP3 inflammasome can promote the release of IL-1β/IL-18 and initiate pyroptosis. Accordingly, the dysregulation of NLRP3 inflammasome activation is involved in a variety of human diseases, including gout, diabetes, and Alzheimer's disease. NLRP3 can sense a variety of structurally unrelated pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) to trigger inflammation, but the unifying mechanism of NLRP3 activation is still poorly understood. Increasing evidence suggests that intracellular ions, such as K + , Ca 2+ , and Cl - , have a significant role in NLRP3 inflammasome activation...
February 13, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29450537/enhanced-expression-of-nlrp3-inflammasome-related-inflammation-in-diabetic-retinopathy
#5
Hui Chen, Xiongze Zhang, Nanying Liao, Lan Mi, Yuting Peng, Bing Liu, Shaochong Zhang, Feng Wen
Purpose: The aim of this study was to determine the association between nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation and disease severity in diabetic retinopathy (DR). Methods: Blood samples were collected from 64 patients with diabetes (DR, 43; without DR, 21) and 25 healthy controls. The protein and mRNA expression levels of NLRP3 inflammasomes in peripheral blood mononuclear cells were determined using western blotting and quantitative real-time reverse transcription-PCR...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29447945/salmeterol-agonist-of-%C3%AE-2-aderenergic-receptor-prevents-systemic-inflammation-via-inhibiting-nlrp3-inflammasome
#6
Nanshan Song, Yinquan Fang, Xiyang Sun, Qingling Jiang, Chenghuan Song, Miaomiao Chen, Jianhua Ding, Ming Lu, Gang Hu
β2-aderenergic receptor (β2AR) agonist, Salmeterol exhibits anti-inflammatory activities. However, the inhibitory effects of Salmeterol on inflammasome activation are elusive and the underlying mechanisms need to be explored. In this study, we established inflammatory model in primary bone marrow-derived macrophages (BMDM) from C57BL/6J mice and β-arrestin2 knockout (β-arrestin2 -/- ) mice in vitro. In vivo study by LPS intraperitoneally (i.p.) in C57BL/6J mice was carried out to ascertain its roles in systemic inflammation...
February 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29446486/interleukin-17a-participates-in-podocyte-injury-by-inducing-il-1%C3%AE-secretion-through-ros-nlrp3-inflammasome-caspase-1-pathway
#7
Junli Yan, Yao Li, Haiping Yang, Li Zhang, Baohui Yang, Mo Wang, Qiu Li
Studies show that the Th17/IL-17A axis plays an important role in the pathogenesis of kidney diseases. Previously, we also showed that IL-17A may play a role in the pathogenesis of primary nephrotic syndrome; however, the underlying mechanism(s) is unclear. The aim of this study was to explore the molecular mechanism of IL-17A inducing podocyte injury in vitro. In this study, the NLRP3 inflammsome activation and the morphology of podocytes were detected by western blot and immunofluorescence .The results showed that podocytes persistently expressed IL-17A receptor, and that NLRP3 inflammasome in these cells was activated upon exposure to IL-17A...
February 15, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29445006/inflammatory-monocytes-drive-influenza-a-virus-mediated-lung-injury-in-juvenile-mice
#8
Bria M Coates, Kelly L Staricha, Clarissa M Koch, Yuan Cheng, Dale K Shumaker, G R Scott Budinger, Harris Perlman, Alexander V Misharin, Karen M Ridge
Healthy children are more likely to die of influenza A virus (IAV) infection than healthy adults. However, little is known about the mechanisms underlying the impact of young age on the development of life-threatening IAV infection. We report increased mortality in juvenile mice compared with adult mice at each infectious dose of IAV. Juvenile mice had sustained elevation of type I IFNs and persistent NLRP3 inflammasome activation in the lungs, both of which were independent of viral titer. Juvenile mice, but not adult mice, had increased MCP-1 levels that remained high even after viral clearance...
February 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29439897/the-elusive-p2x7-macropore
#9
REVIEW
Francesco Di Virgilio, Günther Schmalzing, Fritz Markwardt
ATP, which is released under pathological conditions and is considered a damage-associated molecular pattern (DAMP), activates P2X7 receptors (P2X7Rs), trimeric plasma membrane ion channels selective for small cations. P2X7Rs are partners in NOD-like receptor containing a pyrin (NLRP3) inflammasome activation and promoters of tumor cell growth. P2X7R overstimulation triggers the ATP-dependent opening of a nonselective plasma membrane pore, known as a 'macropore', which allows fluxes of large hydrophilic molecules...
February 10, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29439605/microglial-inflammasome-activation-in-penetrating-ballistic-like-brain-injury
#10
Stephanie W Lee, Shyam Gajavelli, Markus S Spurlock, Cody Andreoni, Juan Pablo de Rivero Vaccari, M Ross Bullock, Robert W Keane, W Dalton Dietrich
Penetrating traumatic brain injury (PTBI) is a significant cause of death and disability in the United States. Inflammasomes are one of the key regulators of the interleukin (IL)-1β mediated inflammatory responses after traumatic brain injury (TBI). However, the contribution of inflammasome signaling after PTBI has not been determined. In this study, adult male Sprague-Dawley rats were subjected to sham procedures or penetrating ballistic-like brain injury (PBBI) and sacrificed at various time points. Tissues were assessed by immunoblot analysis for expression of IL-1β, IL-18 and components of the inflammasome: apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, X-linked inhibitor of apoptosis protein (XIAP), NOD-like receptor protein 3 (NLRP3), and gasdermin-D (GSDMD)...
February 14, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29438905/induction-of-systemic-inflammation-by-hyaluronan-and-hsp70-in-women-with-pre-eclampsia
#11
Mariana Romão-Veiga, Mariana Leticia Matias, Vanessa Rocha Ribeiro, Priscila Rezeck Nunes, Vera Therezinha M Borges, José Carlos Peraçoli, Maria Terezinha S Peraçoli
Pre-eclampsia (PE) is a human pregnancy syndrome with abnormal activation of the innate immune response. The study evaluated the involvement of molecular structures called damage-associated molecular patterns (DAMPs), such as hyaluronan (HA) and heat shock proteins (Hsp) on NLRP1 and NLRP3 inflammasomes activation in peripheral blood monocytes. Twenty pre-eclamptic women, 20 normotensive pregnant women (NT) and 20 non-pregnant women (NP) were studied. Enzyme immunoassay was employed for the determination of HA, Hsp70 and High mobility group Box 1 (HMGB1) in plasma, as well as for the detection of Interleukin-1β (IL-1β), IL-18 and tumor necrosis factor alpha (TNF-α) in the supernatant of monocytes cultured with or without HA and Hsp70...
February 10, 2018: Cytokine
https://www.readbyqxmd.com/read/29437575/saturated-fatty-acids-undergo-intracellular-crystallization-and-activate-the-nlrp3-inflammasome-in-macrophages
#12
Tadayoshi Karasawa, Akira Kawashima, Fumitake Usui-Kawanishi, Sachiko Watanabe, Hiroaki Kimura, Ryo Kamata, Koumei Shirasuna, Yutaro Koyama, Ayana Sato-Tomita, Takashi Matsuzaka, Hiroshi Tomoda, Sam-Yong Park, Naoya Shibayama, Hitoshi Shimano, Tadashi Kasahara, Masafumi Takahashi
OBJECTIVE: Inflammation provoked by the imbalance of fatty acid composition, such as excess saturated fatty acids (SFAs), is implicated in the development of metabolic diseases. Recent investigations suggest the possible role of the NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3) inflammasome, which regulates IL-1β (interleukin 1β) release and leads to inflammation, in this process. Therefore, we investigated the underlying mechanism by which SFAs trigger NLRP3 inflammasome activation...
February 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29434743/anti-depressant-like-effect-of-atractylenolide-i-in-a-mouse-model-of-depression-induced-by-chronic-unpredictable-mild-stress
#13
Haiyan Gao, Xianghua Zhu, Yang Xi, Qun Li, Zhenzhong Shen, Yongjie Yang
Atractylenolide I (AT-I), a major component of the rhizoma of Atractylodes macrocephala Koidz., exerts a wide range of activities. The purpose of the present study was to investigate the anti-depressant-like effect of AT-I in a mouse model of chronic unpredictable mild stress (CUMS), and to explore the possible molecular mechanism involved. It was revealed that AT-I significantly ameliorated CUMS-induced depressive-like behaviors, as evidenced by increased sucrose preference as well as shortened immobility time in the forced swimming and the tail suspension test...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434606/macrophage-recognition-of-crystals-and-nanoparticles
#14
REVIEW
Masafumi Nakayama
Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However, it is unlikely that macrophages have evolutionally acquired receptors specific for crystals or recently emerged nanoparticles...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29434227/the-nlrp3-inflammasome-may-contribute-to-pathologic-neovascularization-in-the-advanced-stages-of-diabetic-retinopathy
#15
Shyam S Chaurasia, Rayne R Lim, Bhav H Parikh, Yeo Sia Wey, Bo Bo Tun, Tien Yin Wong, Chi D Luu, Rupesh Agrawal, Arkasubhra Ghosh, Alessandra Mortellaro, Elizabeth Rackoczy, Rajiv R Mohan, Veluchamy A Barathi
Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, Akimba (Ins2 Akita xVEGF +/- ), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2 Akita ) and Kimba (trVEGF029) mice...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29434214/mesenchymal-stromal-cells-inhibit-nlrp3-inflammasome-activation-in-a-model-of-coxsackievirus-b3-induced-inflammatory-cardiomyopathy
#16
Kapka Miteva, Kathleen Pappritz, Marzena Sosnowski, Muhammad El-Shafeey, Irene Müller, Fengquan Dong, Konstantinos Savvatis, Jochen Ringe, Carsten Tschöpe, Sophie Van Linthout
Inflammation in myocarditis induces cardiac injury and triggers disease progression to heart failure. NLRP3 inflammasome activation is a newly identified amplifying step in the pathogenesis of myocarditis. We previously have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA expression in CVB3-infected mice. ASC protein expression, essential for NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated in MSC-treated mice...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29432801/leptospira-interrogans-infection-leads-to-il-1%C3%AE-and-il-18-secretion-from-a-human-macrophage-cell-line-through-reactive-oxygen-species-and-cathepsin-b-mediated-nlrp3-inflammasome-activation
#17
Shijun Li, Ming Wang, David M Ojcius, Bijun Zhou, Weilin Hu, Ying Liu, Qing Ma, Guangpeng Tang, Dingming Wang, Jie Yan
Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Although there is a large diversity of clinical signs and symptoms, a severe inflammatory response is common to all leptospirosis patients. The mechanism of IL-1βß secretion during Leptospira infection has been previously studied in mouse macrophages. However, the outcome of Leptospira infection is very different in human and murine macrophages, and the mechanisms responsible for IL-1β secretion in human macrophages had not been investigated...
February 9, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29431217/the-role-of-mast-cells-in-autoinflammation
#18
REVIEW
Hanna Bonnekoh, Jörg Scheffel, Naotomo Kambe, Karoline Krause
The concept of autoinflammation was proposed to define a new class of immune disorders categorized by self-directed inflammation that is driven via activation of innate immune pathways. Within innate immunity, inflammasomes serve as intracellular signaling platforms to endogenous danger molecules and pathogens. Their key function is the cleavage of pro-interleukin-1β (pro-IL-1β) into its active form to promote inflammation and programmed cell death. A growing number of inflammasome sensors were described, among which NLR family pyrin domain containing 3 (NLRP3) is the best-studied sensor...
March 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29430721/association-of-the-nod-like-receptor-3-nlrp3-gene-variability-with-recurrent-aphthous-stomatitis-in-the-czech-population
#19
Simona Slezakova, Petra Borilova Linhartova, Lucie Masopustova, Jirina Bartova, Jitka Petanova, Pavel Kuklinek, Antonin Fassmann, Ladislav Dusek, Lydie Izakovicova Holla
BACKGROUND: Recurrent aphthous stomatitis (RAS) is a multifactorial disease with unclear etiopathogenesis in which disturbance of immunological processes maybe involved. The aim of our study was to investigate three single nucleotide polymorphisms (SNPs) rs3806265, rs4612666, rs10754558 in NOD-like receptor 3 (NLRP3), the gene encoding the component of inflammasome, in patients with RAS and healthy controls in the Czech population. METHODS: A total of 207 subjects were included in this case-control study...
February 12, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29426321/systemic-autoinflammation-with-intractable-epilepsy-managed-with-interleukin-1-blockade
#20
Allen D DeSena, Thuy Do, Grant S Schulert
BACKGROUND: Autoinflammatory disorders are distinguished by seemingly random episodes of systemic hyperinflammation, driven in particular by IL-1. Recent pre-clinical work has shown a key role for IL-1 in epilepsy in animal models, and therapies for autoinflammation including IL-1 blockade are proposed for refractory epilepsy. CASE PRESENTATION: Here, we report an adolescent female with signs of persistent systemic inflammation and epilepsy unresponsive to multiple anti-epileptic drugs (AED)...
February 9, 2018: Journal of Neuroinflammation
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