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https://www.readbyqxmd.com/read/28533778/dnase1l3-regulates-inflammasome-dependent-cytokine-secretion
#1
Guilan Shi, Kennady N Abbott, Wenbo Wu, Russell D Salter, Peter A Keyel
Pediatric-onset systemic lupus erythematosus arises in humans and mice lacking the endonuclease Dnase1L3. When Dnase1L3 is absent, DNA from circulating apoptotic bodies is not cleared, leading to anti-DNA antibody production. Compared to early anti-DNA and anti-chromatin responses, other autoantibody responses and general immune activation in Dnase1L3(-/-) mice are greatly delayed. We investigated the possibility that immune activation, specifically inflammasome activation, is regulated by Dnase1L3. Here, we report that Dnase1L3 inhibition blocked both NLR family, pyrin domain containing 3 (NLRP3) and NLRC4 inflammasome-mediated release of high-mobility group box 1 protein and IL-1β...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28516117/reconstruction-of-the-mouse-inflammasome-system-in-hek293t-cells
#2
Hexin Shi, Anne Murray, Bruce Beutler
The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and the protein kinase NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et al., 2016). When cells are exposed to microbes and/or danger signals, the inflammasome assembles and serves as a platform for the activation of caspase-1. Caspase-1 activation promotes the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and IL-33 as well as pyroptosis induction (Gross et al...
November 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28516116/asc-particle-induced-peritonitis
#3
Lucia de Almeida, Andrea Dorfleutner, Christian Stehlik
In response to pathogen infection and tissue damage, inflammasome sensors such as NLRP3 and AIM2 are activated, which triggers PYRIN domain (PYD)-mediated ASC nucleation, followed by self-perpetuating ASC polymerization, which ultimately culminates in caspase-1 activation, interleukin (IL)-1β and IL-18 processing and release and pyroptosis (Ratsimandresy et al., 2013; Cai et al., 2014). Inflammasomes release not only cytokines, but also the polymeric ASC danger particles (pASC) by pyroptosis, which perpetuate and propagate inflammasome responses to bystander cells to engage cell intrinsic ASC and caspase-1 (Baroja-Mazo et al...
October 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515391/advanced-glycation-end-products-regulate-interleukin-1%C3%AE-production-in-human-placenta
#4
Kotomi Seno, Saoko Sase, Ayae Ozeki, Hironori Takahashi, Akihide Ohkuchi, Hirotada Suzuki, Shigeki Matsubara, Hisataka Iwata, Takehito Kuwayama, Koumei Shirasuna
Maternal obesity is a major risk factor for pregnancy complications, causing inflammatory cytokine release in the placenta, including interleukin-1β (IL-1β), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic and placental inflammation with elevated circulating advanced glycation end products (AGEs). IL-1β is a pivotal inflammatory cytokine associated with obesity and pregnancy complications, and its production is regulated by NLR family pyrin domain-containing 3 (NLRP3) inflammasomes...
May 18, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28507179/elevated-expression-of-the-nlrp3-inflammasome-and-its-correlation-with-disease-activity-in-adult-onset-still-disease
#5
Chia-Wei Hsieh, Yi-Ming Chen, Chi-Chen Lin, Kuo-Tung Tang, Hsin-Hua Chen, Wei-Ting Hung, Kuo-Lung Lai, Der-Yuan Chen
OBJECTIVE: The dysregulation of the NLRP3 (NLR containing a pyrin domain) inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease (AOSD) is regarded as an autoinflammatory disease. However, the pathogenic involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in AOSD are currently unknown. METHODS: The mRNA expression of NLRP3 inflammasome signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD and 14 healthy subjects was determined using quantitative-PCR (qPCR)...
May 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28500395/the-human-serum-protein-c4b-binding-protein-inhibits-pancreatic-iapp-induced-inflammasome-activation
#6
Klaudia Kulak, Gunilla T Westermark, Nikolina Papac-Milicevic, Erik Renström, Anna M Blom, Ben C King
AIMS/HYPOTHESIS: Inflammasome activation and subsequent IL-1β production is a driver of islet pathology in type 2 diabetes. Oligomers, but not mature amyloid fibrils, of human islet amyloid polypeptide (IAPP), which is co-secreted with insulin, trigger NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome activation. C4b-binding protein (C4BP), present in serum, binds to IAPP and affects transition of IAPP monomers and oligomers to amyloid fibrils. We therefore hypothesised that C4BP inhibits IAPP-mediated inflammasome activation and IL-1β production...
May 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28493895/the-cardiac-glycoside-ouabain-activates-nlrp3-inflammasomes-and-promotes-cardiac-inflammation-and-dysfunction
#7
Motoi Kobayashi, Fumitake Usui-Kawanishi, Tadayoshi Karasawa, Hiroaki Kimura, Sachiko Watanabe, Nathan Mise, Fujio Kayama, Tadashi Kasahara, Naoyuki Hasebe, Masafumi Takahashi
Cardiac glycosides such as digoxin are Na+/K+-ATPase inhibitors that are widely used for the treatment of chronic heart failure and cardiac arrhythmias; however, recent epidemiological studies have suggested a relationship between digoxin treatment and increased mortality. We previously showed that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes, which regulate caspase-1-dependent interleukin (IL)-1β release, mediate the sterile cardiovascular inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28486969/activation-of-p2x7-receptor-and-nlrp3-inflammasome-assembly-in-hippocampal-glial-cells-mediates-chronic-stress-induced-depressive-like-behaviors
#8
Na Yue, Huijie Huang, Xiaocang Zhu, Qiuqin Han, Yalin Wang, Bing Li, Qiong Liu, Gencheng Wu, Yuqiu Zhang, Jin Yu
BACKGROUND: In recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28481474/instant-hydrogelation-inspired-by-inflammasomes
#9
Huaimin Wang, Zhaoqianqi Feng, Alvin Lu, Yujie Jiang, Hao Wu, Bing Xu
Based on the recent structures of the PYRIN domain of ASC in the protein filament of inflammasomes and the observation that pyridoxal phosphate (P5P) modulates the self-assembly of ASC, we rationally designed an N-terminal capped nonapeptide (Nap-FFKKFKLKL, 1) to form supramolecular nanofibers consisting of α-helix. The addition of P5P to the solution of 1 results in a hydrogel almost instantly (about 4 seconds). Several other endogenous small molecules (e.g., pyridoxal, folinic acid, ATP, and AMP) also convert the solution of 1 to a hydrogel...
May 8, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28470940/p2x7-receptor-inhibition-attenuated-sympathetic-nerve-sprouting-after-myocardial-infarction-via-the-nlrp3-il-1%C3%AE-pathway
#10
Jie Yin, Yu Wang, Hesheng Hu, Xiaolu Li, Mei Xue, Wenjuan Cheng, Ye Wang, Xinran Li, Na Yang, Yugen Shi, Suhua Yan
Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X7 signal has been shown to activate the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X7 signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin-1β (IL-1β) axis is involved in the process...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28465656/resolvin-d1-inhibits-inflammatory-response-in-stz-induced-diabetic-retinopathy-rats-possible-involvement-of-nlrp3-inflammasome-and-nf-%C3%AE%C2%BAb-signaling-pathway
#11
Yizhou Yin, Fei Chen, Wenyan Wang, Han Wang, Xuedong Zhang
PURPOSE: To investigate the effect of resolvin D1 (RvD1) on the Nod-like receptor family pyrin domain-containing (NLRP3) inflammasome and the nuclear factor-kappa beta (NF-κB) pathway in streptozotocin (STZ)-induced diabetic retinopathy in rats. METHODS: Ninety-six male rats were divided into four groups: control, STZ, RvD1, and vehicle. The rats with diabetic retinopathy induced by STZ in the RvD1 and vehicle groups were given an intravitreal injection of RvD1 (1,000 ng/kg) or the same dosage of vehicle, respectively...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28465465/nlrp3-inflammasome-assembly-is-regulated-by-phosphorylation-of-the-pyrin-domain
#12
Andrea Stutz, Carl-Christian Kolbe, Rainer Stahl, Gabor L Horvath, Bernardo S Franklin, Olivia van Ray, Rebecca Brinkschulte, Matthias Geyer, Felix Meissner, Eicke Latz
NLRP3 is a cytosolic pattern recognition receptor that senses microbes and endogenous danger signals. Upon activation, NLRP3 forms an inflammasome with the adapter ASC, resulting in caspase-1 activation, release of proinflammatory cytokines and cell death. How NLRP3 activation is regulated by transcriptional and posttranslational mechanisms to prevent aberrant activation remains incompletely understood. Here, we identify three conserved phosphorylation sites in NLRP3 and demonstrate that NLRP3 activation is controlled by phosphorylation of its pyrin domain (PYD)...
May 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28460353/baicalin-ameliorates-chronic-unpredictable-mild-stress-induced-depressive-behavior-involving-the-inhibition-of-nlrp3-inflammasome-activation-in-rat-prefrontal-cortex
#13
Xiaoxin Liu, Chao Liu
Abnormal activation of nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome could induce inflammation in the central nervous system and result in the hyperactivity of HPA axis, which were involved in the pathophysiology of depression. Baicalin, a major polyphenol compound extracts from Scutellaria radix roots, has been previously confirmed to normalize the hyperactivity of HPA axis in rats received chronic mild stress. However, its antidepressant effects and mechanisms are remains unclear in chronic unpredictable mild stress (CUMS) model of depression...
April 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28455230/mangiferin-attenuates-blast-induced-traumatic-brain-injury-via-inhibiting-nlrp3-inflammasome
#14
Kaihua Fan, Jie Ma, Wenjing Xiao, Jingmin Chen, Juan Wu, Jiandong Ren, Jun Hou, Yonghe Hu, Jianwen Gu, Botao Yu
There is growing evidence that Mangiferin possess therapeutic benefit during neuroinflammation on various brain injury models due to its anti-inflammatory properties. It is reported that inflammatory plays a crucial role in the pathogenesis of secondary injury induced by the blast-induced traumatic brain injury (bTBI). However, the role of mangiferin in bTBI is yet to be studied. In our study, the potential effect of mangiferin in the duration of bTBI was examined first. Fortunately, the amelioration of cerebral cortex damage was found in rats suffering bTBI after mangiferin administration...
April 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28428961/glucose-insulin-potassium-alleviates-intestinal-mucosal-barrier-injuries-involving-decreased-expression-of-uncoupling-protein-2-and-nlr-family-pyrin-domain-containing-3-inflammasome-in-polymicrobial-sepsis
#15
Jun-Liang Zhang, Yi-Ting Chen, Guang-Dao Chen, Tao Wang, Ju-Xin Zhang, Qi-Yi Zeng
Uncoupling protein 2 (UCP2) may be critical for intestinal barrier function which may play a key role in the development of sepsis, and insulin has been reported to have anti-inflammatory effects. Male Sprague-Dawley rats were randomly allocated into five groups: control group, cecal ligation and puncture (CLP) group, sham surgery group, CLP plus glucose-insulin-potassium (GIK) group, and CLP plus glucose and potassium (GK) group. Ileum tissues were collected at 24 h after surgery. Histological and cytokine analyses, intestinal permeability tests, and western blots of intestinal epithelial tight junction component proteins and UCP2 were performed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28420787/activation-of-nlrp3-inflammasome-complex-potentiates-venous-thrombosis-in-response-to-hypoxia
#16
Neha Gupta, Anita Sahu, Amit Prabhakar, Tathagata Chatterjee, Tarun Tyagi, Babita Kumari, Nilofar Khan, Velu Nair, Nitin Bajaj, Manish Sharma, Mohammad Zahid Ashraf
Venous thromboembolism (VTE), caused by altered hemostasis, remains the third most common cause of mortality among all cardiovascular conditions. In addition to established genetic and acquired risk factors, low-oxygen environments also predispose otherwise healthy individuals to VTE. Although disease etiology appears to entail perturbation of hemostasis pathways, the key molecular determinants during immediate early response remain elusive. Using an established model of venous thrombosis, we here show that systemic hypoxia accelerates thromboembolic events, functionally stimulated by the activation of nucleotide binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome complex and increased IL-1β secretion...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28404641/nlrp3-inflammasome-as-a-novel-target-for-docosahexaenoic-acid-metabolites-to-abrogate-glomerular-injury
#17
Guangbi Li, Zhida Chen, Owais M Bhat, Qinghua Zhang, Justine M Abais-Battad, Sabena M Conley, Joseph K Ritter, Pin-Lan Li
The NOD-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been implicated in podocyte injury and glomerular sclerosis during hyperhomocysteinemia (hHcys). However, it remains unclear whether NLRP3 inflammasome can be a therapeutic target for treatment of hHcys-induced kidney injury. Given that docosahexaenoic acid (DHA) metabolites-resolvins have potent anti-inflammatory effects, the present study tested whether the prototype resolvin D1 (RvD1) and 17S-hydroxy DHA (17S-HDHA), an intermediate product abrogate hHcys-induced podocyte injury by targeting the NLRP3 inflammasome...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28401330/cordycepin-confers-neuroprotection-in-mice-models-of-intracerebral-hemorrhage-via-suppressing-nlrp3-inflammasome-activation
#18
Yijun Cheng, Yongxu Wei, Wenlei Yang, Yaying Song, Hanbing Shang, Yu Cai, Zhebao Wu, Weiguo Zhao
Neuroinflammation has been recognized as a major contributor to brain injury caused by intracerebral hemorrhage (ICH). Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome acts as an important mediator of inflammatory response in various inflammation-related diseases including hemorrhagic insults. Cordycepin has recently been shown to possess anti-inflammatory effect; however, its role and the possible underlying mechanisms in ICH remain unclear. This study was designed to investigate the neuroprotective effect of cordycepin in mice models of ICH and to elucidate the underlying molecular mechanisms...
April 11, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28386255/familial-mediterranean-fever-recent-developments-in-pathogenesis-and-new-recommendations-for-management
#19
REVIEW
Seza Özen, Ezgi Deniz Batu, Selcan Demir
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28378341/nlrp3-inflammasome-induced-liver-graft-injury-through-activation-of-telomere-independent-rap1-kc-axis
#20
Hui Liu, Oscar Wai Ho Yeung, Chang Xian Li, Xiao Bing Liu, Xiang Qi, Kevin Tak Pan Ng, Jiang Liu, Yuen Yuen Ma, Yin Fan Lam, Qizhou Lian, See Ching Chan, Chung Mau Lo, Kwan Man
Acute phase inflammation plays a critical role in liver graft injury. Inflammasomes, multi-molecular complexes in the cytoplasm, are responsible for initiating inflammation. Here, we aimed to explore the role of inflammasomes in liver graft injury and further to investigate the regulatory mechanism. In a clinical liver transplant cohort, we found that intragraft expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes was significantly up-regulated post-transplantation...
April 5, 2017: Journal of Pathology
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