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Inflammasome phosphorylation

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https://www.readbyqxmd.com/read/29318480/rosmarinic-acid-mitigates-lipopolysaccharide-induced-neuroinflammatory-responses-through-the-inhibition-of-tlr4-and-cd14-expression-and-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#1
Yicong Wei, Jianxiong Chen, Yonghong Hu, Wei Lu, Xiaoqin Zhang, Ruiguo Wang, Kedan Chu
The excessive activation of microglia plays a key role in the pathogenesis of neurodegenerative diseases. The neuroprotective properties of rosmarinic acid have been reported in a variety of disease models both in vitro and in vivo; however, the mechanism underlying its anti-neuroinflammatory activity has not been clearly elucidated. In the present study, we evaluated the anti-inflammatory effects of rosmarinic acid in conditions of neuroinflammatory injury in vitro and in vivo. The results indicated that rosmarinic acid reduced the expression of CD11b, a marker of microglia and macrophages, in the brain and dramatically inhibited the levels of inflammatory cytokines and mediators, such as TNFα, IL-6, IL-1β, COX-2, and iNOS, in a dose-dependent manner both in vitro and in vivo...
January 9, 2018: Inflammation
https://www.readbyqxmd.com/read/29273951/neuroinflammatory-responses-in-alzheimer-s-disease
#2
REVIEW
Cira Dansokho, Michael Thomas Heneka
Neuroinflammatory responses in Alzheimer's disease (AD) are complex and not fully understood. They involve various cellular and molecular players and associate interaction between the central nervous system (CNS) and the periphery. Amyloid peptides within the senile plaques and abnormally phosphorylated tau in neurofibrillary tangles are able to initiate inflammatory responses, in brain of AD patients and in mouse models of this disease. The outcome of these responses on the pathophysiology of AD depends on several factors and can be either beneficial or detrimental...
December 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29273596/dihydrolipoic-acid-inhibits-lysosomal-rupture-and-nlrp3-through-lysosome-associated-membrane-protein-1-calcium-calmodulin-dependent-protein-kinase-ii-tak1-pathways-after-subarachnoid-hemorrhage-in-rat
#3
Keren Zhou, Budbazar Enkhjargal, Zhiyi Xie, Chengmei Sun, Lingyun Wu, Jay Malaguit, Sheng Chen, Jiping Tang, Jianmin Zhang, John H Zhang
BACKGROUND AND PURPOSE: The NLRP3 (nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a crucial component of the inflammatory response in early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated a role of dihydrolipoic acid (DHLA) in lysosomal rupture, NLRP3 activation, and determined the underlying pathway. METHODS: SAH was induced by endovascular perforation in male Sprague-Dawley rats...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29259897/pioglitazone-ameliorates-retinal-ischemia-reperfusion-injury-via-suppressing-nlrp3-inflammasome-activities
#4
Yue-Lu Zhang, Ruo-Bing Wang, Wei-Yi Li, Fang-Zhou Xia, Lin Liu
AIM: To explore the role of Pioglitazone (Pio) on a mouse model of retinal ischemia/reperfusion (I/R) injury and to elucidate the potential mechanism. METHODS: Retinal ischemia was induced in mice by increasing the intraocular pressure, and Pio was administered 4h though periocular injection before I/R. The number of cells in the ganglion cell layer (GCL) was counted 7d after retinal I/R injury. Glial fibrillary acidic protein (GFAP), nuclear factor-kappa B (NF-κB), p38, phosphorylated-p38, PPAR-γ, interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), NLRP3, cleaved caspase-1, caspase-1 were determined by real-time polymerase chain reaction and Western blotting...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29240643/temporally-distinct-regulation-of-pathways-contributing-to-cardiac-proteostasis-during-the-acute-and-recovery-phases-of-sepsis
#5
Kristen T Crowell, Samantha Moreno, Jennifer L Steiner, Catherine S Coleman, David I Soybel, Charles H Lang
BACKGROUND: Cardiac dysfunction is a common manifestation of sepsis and is associated with early increases in inflammation and decreases in myocardial protein synthesis. However, little is known regarding the molecular mechanisms regulating protein homeostasis during the recovery phase after the removal of the septic nidus. Therefore, the purpose of this study was to investigate diverse signal transduction pathways that regulate myocardial protein synthesis and degradation. METHODS: Adult male C57BL/6 mice were used to identify potential mechanisms mediating the acute (24 h) effect of cecal ligation and puncture (CLP) as well as long-term changes that manifest during the chronic (10 d) recovery phase...
December 13, 2017: Shock
https://www.readbyqxmd.com/read/29222907/the-ameliorative-effect-of-fluoxetine-on-neuroinflammation-induced-by-sleep-deprivation
#6
Maosheng Xia, Xiaowei Li, Li Yang, Jiaan Ren, Guangfeng Sun, Shuang Qi, Alexei Verkhratsky, Baoman Li
It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29203393/pyrin-inflammasome-regulates-tight-junction-integrity-to-restrict-colitis-and-tumorigenesis
#7
Deepika Sharma, Ankit Malik, Clifford S Guy, Rajendra Karki, Peter Vogel, Thirumala-Devi Kanneganti
BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) increase risk for colorectal cancer. Mutations in the Mediterranean fever gene (MEFV or pyrin) are associated with hereditary autoinflammatory disease and severe IBD. Expression of MEFV, a sensor protein that the initiates assembly of the inflammasome complex, is increased in colon biopsies from patients with IBD. We investigated the role of pyrin in intestinal homeostasis in mice. METHODS: Mefv-/- mice and C57/BL6 mice (controls) were given azoxymethane followed by multiple rounds of dextran sodium sulfate (DSS) to induce colitis and tumorigenesis...
December 1, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29178967/blocking-atp-sensitive-potassium-channel-alleviates-morphine-tolerance-by-inhibiting-hsp70-tlr4-nlrp3-mediated-neuroinflammation
#8
Jie Qu, Xue-You Tao, Peng Teng, Yan Zhang, Ci-Liang Guo, Liang Hu, Yan-Ning Qian, Chun-Yi Jiang, Wen-Tao Liu
BACKGROUND: Long-term use of morphine induces analgesic tolerance, which limits its clinical efficacy. Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. In our study, we investigated whether other existing alternative pathways caused morphine-induced activation of TLR4 in microglia. We focused on heat shock protein 70 (HSP70), a damage-associated molecular pattern (DAMP), which was released from various cells upon stimulations under the control of KATP channel and bound with TLR4-inducing inflammation...
November 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29170442/inhibition-of-the-inflammatory-response-to-stress-by-targeting-interaction-between-pkr-and-its-cellular-activator-pact
#9
Stephanie Dabo, Patrick Maillard, Milagros Collados Rodriguez, Marianne Doré Hansen, Sabrina Mazouz, Donna-Joe Bigot, Marion Tible, Geneviève Janvier, Olivier Helynck, Patricia Cassonnet, Yves Jacob, Jacques Bellalou, Anne Gatignol, Rekha C Patel, Jacques Hugon, Hélène Munier-Lehmann, Eliane F Meurs
PKR is a cellular kinase involved in the regulation of the integrative stress response (ISR) and pro-inflammatory pathways. Two N-terminal dsRNA Binding Domains (DRBD) are required for activation of PKR, by interaction with either dsRNA or PACT, another cellular DRBD-containing protein. A role for PKR and PACT in inflammatory processes linked to neurodegenerative diseases has been proposed and raised interest for pharmacological PKR inhibitors. However, the role of PKR in inflammation is subject to controversy...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29164996/cptp-a-sphingolipid-transfer-protein-that-regulates-autophagy-and-inflammasome-activation
#10
Shrawan Kumar Mishra, Yong-Guang Gao, Yibin Deng, Charles E Chalfant, Edward H Hinchcliffe, Rhoderick E Brown
The macroautophagy/autophagy and inflammasome pathways are linked through their roles in innate immunity and chronic inflammatory disease. Ceramide-1-phosphate (C1P) is a bioactive sphingolipid that regulates pro-inflammatory eicosanoid production. Whether C1P also regulates autophagy and inflammasome assembly/activation is not known. Here we show that CPTP (a protein that traffics C1P from its site of phosphorylation in the trans-Golgi to target membranes) regulates both autophagy and inflammasome activation...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29163487/baicalin-inhibits-nod-like-receptor-family-pyrin-containing-domain-3-inflammasome-activation-in-murine-macrophages-by-augmenting-protein-kinase-a-signaling
#11
Chen-Guang Li, Liang Yan, Feng-Yi Mai, Zi-Jian Shi, Li-Hui Xu, Yan-Yun Jing, Qing-Bing Zha, Dong-Yun Ouyang, Xian-Hui He
The flavonoid baicalin has been reported to possess potent anti-inflammatory activities by suppressing inflammatory signaling pathways. However, whether baicalin can suppress the activation of NOD-like receptor (NLR) family, pyrin containing domain 3 (NLRP3) inflammasome in macrophages is largely unknown. Here, we showed that baicalin treatment dose-dependently inhibited adenosine triphosphate (ATP) or nigericin-induced NLRP3 inflammasome activation, as revealed by the decreased release of mature interleukin (IL)-1β, active caspase-1p10, and high-mobility group box-1 protein from lipopolysaccharide (LPS)-primed bone marrow-derived macrophages...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163427/antimycobacterial-and-anti-inflammatory-mechanisms-of-baicalin-via-induced-autophagy-in-macrophages-infected-with-mycobacterium-tuberculosis
#12
Qingwen Zhang, Jinxia Sun, Yuli Wang, Weigang He, Lixin Wang, Yuejuan Zheng, Jing Wu, Ying Zhang, Xin Jiang
Tuberculosis (TB) remains a leading killer worldwide among infectious diseases and the effective control of TB is still challenging. Autophagy is an intracellular self-digestion process which has been increasingly recognized as a major host immune defense mechanism against intracellular microorganisms like Mycobacterium tuberculosis (Mtb) and serves as a key negative regulator of inflammation. Clinically, chronic inflammation surrounding Mtb can persist for decades leading to lung injury that can remain even after successful treatment...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29156799/asiatic-acid-protects-against-hepatic-ischemia-reperfusion-injury-by-inactivation-of-kupffer-cells-via-ppar%C3%AE-nlrp3-inflammasome-signaling-pathway
#13
Ying Xu, Jun Yao, Chen Zou, Heng Zhang, Shouliang Zhang, Jun Liu, Gui Ma, Pengcheng Jiang, Wenbo Zhang
Hepatic ischemia/reperfusion (I/R) contributes to major complications in clinical practice affecting perioperative morbidity and mortality. Recent evidence suggests the key role of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammaosme activation on the pathogenesis of I/R injury. Asiatic acid (AA) is a pentacyclic triterpene derivative presented with versatile activities, including antioxidant, anti-inflammation and hepatoprotective effects. This study was designed to determine whether AA had potential hepatoprotective benefits against hepatic I/R injury, as well as to unveil the underlying mechanisms involved in the putative effects...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29141025/suppression-of-inflammatory-and-infection-responses-in-lung-macrophages-by-eucalyptus-oil-and-its-constituent-1-8-cineole-role-of-pattern-recognition-receptors-trem-1-and-nlrp3-the-map-kinase-regulator-mkp-1-and-nf%C3%AE%C2%BAb
#14
Niket Yadav, Harish Chandra
Eucalyptus oil (EO) used in traditional medicine continues to prove useful for aroma therapy in respiratory ailments; however, there is a paucity of information on its mechanism of action and active components. In this direction, we investigated EO and its dominant constituent 1,8-cineole (eucalyptol) using the murine lung alveolar macrophage (AM) cell line MH-S. In an LPS-induced AM inflammation model, pre-treatment with EO significantly reduced (P ≤0.01or 0.05) the pro-inflammatory mediators TNF-α, IL-1 (α and β), and NO, albeit at a variable rate and extent; 1,8-cineole diminished IL-1 and IL-6...
2017: PloS One
https://www.readbyqxmd.com/read/29140564/%C3%AE-catenin-and-il-1%C3%AE-dependent-cxcl10-production-drives-progression-of-disease-in-a-mouse-model-of-congenital-hepatic-fibrosis
#15
Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Congenital Hepatic Fibrosis (CHF), a genetic disease caused by mutations in the PKHD1 gene, encoding for the protein fibrocystin (FPC), is characterized by biliary dysgenesis, progressive portal fibrosis, and by a PKA-mediated activating phosphorylation of β-Catenin at Ser675. Biliary structures of Pkhd1(del4/del4) mice, a mouse model of CHF, secrete CXCL10 a chemokine able to recruit macrophages. The aim of this study is to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/CD and to understand the mechanisms leading to increased CXCL10 secretion...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29103703/anti-inflammatory-capacity-of-lactobacillus-rhamnosus-gg-in-monophasic-variant-salmonella-infected-piglets-is-correlated-with-impeding-nlrp6-mediated-host-inflammatory-responses
#16
Jiao Yu, Yao-Hong Zhu, Gui-Yan Yang, Wei Zhang, Dong Zhou, Jin-Hui Su, Jiu-Feng Wang
In this study, we investigated the effect of Lactobacillus rhamnosus GG strain (LGG) in ameliorating enteritis in newly weaned pigs following challenge with a monophasic variant of Salmonella enterica serovar Typhimurium (serotyped as 4,[5],12:i:-), which has been linked to disease in humans and livestocks over the past 10 years. In weaned pigs, S. enterica serovar 4,[5],12:i:- induced the mRNA expression of toll like receptor (TLR) 5 and TLR4, while increasing interleukin (IL)-8 and IL-6 mRNA expression in the jejunum...
October 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28970254/silybin-inhibits-nlrp3-inflammasome-assembly-through-the-nad-sirt2-pathway-in-mice-with-nonalcoholic-fatty-liver-disease
#17
Bangling Zhang, Dan Xu, Linlin She, Zixia Wang, Na Yang, Runbin Sun, Yirui Zhang, Caixia Yan, Qingli Wei, Jiye Aa, Baolin Liu, Guangji Wang, Yuan Xie
Silybin is one of the effective, traditional Chinese medicines used as a hepatoprotective agent in nonalcoholic fatty liver disease (NAFLD) therapy worldwide, and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been recognized as an important factor involved in NAFLD development. However, little is known about the mechanisms of silybin in the regulation of high-fat diet (HFD)-induced liver inflammation. In our study, we found that silybin inhibited endoplasmic reticulum stress and NLRP3 inflammasome activation in the livers of HFD-fed mice and in cultured hepatocytes...
September 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28968864/atm-activated-autotaxin-atx-propagates-inflammation-and-dna-damage-in-lung-epithelial-cells-a-new-mode-of-action-for-silica-induced-dna-damage
#18
Huiyuan Zheng, Johan Högberg, Ulla Stenius
Silica exposure is a common risk factor for lung cancer. It has been claimed that key elements in cancer development are activation of inflammatory cells that indirectly induce DNA damage and proliferative stimuli in respiratory epithelial cells. We studied DNA damage induced by silica particles in respiratory epithelial cells and focused the role of the signaling enzyme autotaxin (ATX). A549 and 16HBE lung epithelial cells were exposed silica particles. Reactive oxidative species (ROS), NLRP3 inflammasome activation, ATX, ataxia telangiectasia mutated (ATM), and DNA damage (γH2AX, pCHK1, pCHK2, comet assay) were endpoints...
September 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28966691/wogonoside-alleviates-inflammation-induced-by-traumatic-spinal-cord-injury-by-suppressing-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#19
Yonglin Zhu, Hanzhong Zhu, Zhaojie Wang, Fengguang Gao, Jingsheng Wang, Wenqiang Zhang
Wogonoside possesses anti-oxidative, anti-inflammatory, anti-allergy and anti-tumor properties. The aim of the present study was to evaluate whether wogonoside alleviates spinal cord injury (SCI)-induced inflammation via nuclear factor (NF)-κB and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation. Sprague-Dawley rats were positioned in the jaws of a calibrated aneurysm clip with a closing pressure of 55 g. The jaws were placed on the dorsal and ventral surfaces of the spinal cord and left in place for 1 min...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28943315/nlrp3-phosphorylation-is-an-essential-priming-event-for-inflammasome-activation
#20
Nan Song, Zhao-Shan Liu, Wen Xue, Zhao-Fang Bai, Qian-Yi Wang, Jiang Dai, Xin Liu, Yi-Jiao Huang, Hong Cai, Xiao-Yan Zhan, Qiu-Ying Han, Hongxia Wang, Yuan Chen, Hui-Yan Li, Ai-Ling Li, Xue-Min Zhang, Tao Zhou, Tao Li
Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation...
October 5, 2017: Molecular Cell
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