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Inflammasome phosphorylation

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28942022/x-11-5-27-a-daidzein-derivative-inhibits-nlrp3-inflammasome-activity-via-promoting-autophagy
#9
Wei Zhou, Xiuting Liu, Kunpeng Cheng, Xin Zhang, Jinrong Lu, Rong Hu
NLRP3 inflammasome is a cytoplasmic multiprotein complex which plays a critical role in response to infection or injury, however, aberrant NLRP3 inflammasome activation is deleterious. In our study, we investigate the inhibitory effect of X-11-5-27, a daidzein derivative, on the NLRP3 inflammasome. The results showed that the activation of NLRP3 inflammasome was inhibited by X-11-5-27 in a dose-dependent manner, followed by a decrease in the cleavage of caspase-1 and maturation of IL-1β. Furthermore, we found that X-11-5-27 significantly restrained the formation of NLRP3 inflammasome...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#10
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28928791/wu-mei-wan-reduces-insulin-resistance-via-inhibition-of-nlrp3-inflammasome-activation-in-hepg2-cells
#11
Xueping Yang, Lingli Li, Ke Fang, Ruolan Dong, Jingbin Li, Yan Zhao, Hui Dong, Ping Yi, Zhaoyi Huang, Guang Chen, Fuer Lu
Wu-Mei-Wan (WMW) is a Chinese herbal formula used to treat type 2 diabetes. In this study, we aimed to explore the effects and mechanisms of WMW on insulin resistance in HepG2 cells. HepG2 cells were pretreated with palmitate (0.25 mM) to impair the insulin signaling pathway. Then, they were treated with different doses of WMW-containing medicated serum and stimulated with 100 nM insulin. Results showed that palmitate could reduce the glucose consumption rate in HepG2 cells and impair insulin signaling related to phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), thereby regulating the downstream signaling pathways...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28921464/posttranslational-modification-control-of-inflammatory-signaling
#12
Yibo Si, Yunlu Zhang, Zijuan Chen, Ruixue Zhou, Yihua Zhang, Doudou Hao, Dapeng Yan
Inflammation is usually the defensive reaction of the immune system to the invasion of pathogen and the exogenous objects. The activation of inflammation helps our body to eliminate pathogenic microbe, virus, and parasite harming our health, while under many circumstances inflammation is the direct cause of the pathological damage in tissues and dysfunction of organs. The posttranslational modification (PTM) of the inflammatory pathways, such as TLR pathways, RLR pathways, NLR pathway, intracellular DNA sensors, intracellular RNA sensors, and inflammasomes, is crucial in the regulation of these signaling trails...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28878677/teuvincenone-f-suppresses-lps-induced-inflammation-and-nlrp3-inflammasome-activation-by-attenuating-nemo-ubiquitination
#13
Xibao Zhao, Debing Pu, Zizhao Zhao, Huihui Zhu, Hongrui Li, Yaping Shen, Xingjie Zhang, Ruihan Zhang, Jianzhong Shen, Weilie Xiao, Weilin Chen
Inflammation causes many diseases that are serious threats to human health. However, the molecular mechanisms underlying regulation of inflammation and inflammasome activation are not fully understood which has delayed the discovery of new anti-inflammatory drugs of urgent clinic need. Here, we found that the natural compound Teuvincenone F, which was isolated and purified from the stems and leaves of Premna szemaoensis, could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines production and NLRP3 inflammasome activation...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28870124/reactive-oxygen-species-trigger-nf-%C3%AE%C2%BAb-mediated-nlrp3-inflammasome-activation-induced-by-zinc-oxide-nanoparticles-in-a549-cells
#14
Xiao Liang, Di Zhang, Wenjia Liu, Yingjie Yan, Fang Zhou, Weidong Wu, Zhen Yan
Inhaled zinc oxide nanoparticles (ZnO-NPs) induce lung inflammation associated with oxidative stress. The NLRP3 inflammasome plays a pivotal role in the development of lung inflammation. However, the underlying effects of the NLRP3 inflammasome on ZnO-NPs-induced inflammation remain obscure. In the present study, reactive oxygen species (ROS) generation, expression of NLRP3, caspase-1 p10, and cytokines release of interleukin (IL)-1β and IL-18 were determined after A549 cells were exposed to ZnO-NPs. The ROS scavenger N-acetyl-L-cysteine (NAC), nuclear factor kappa B (NF-κB inhibitor BAY11-7082, and NLRP3 inhibitor glibenclamide (GEL) were used to explore the mechanism of NLRP3 inflammasome activation-induced by ZnO-NPs...
October 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/28843178/esculentoside-a-exerts-anti-inflammatory-activity-in-microglial-cells
#15
Hui Yang, Yijian Chen, Linjie Yu, Yun Xu
Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. This study was designed to evaluate the pharmacological effects of EsA on lipopolysaccharide (LPS)-stimulated BV2 microglia and primary microglia cells. Our results indicated that EsA pretreatment significantly decreased LPS-induced production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) and impeded LPS-mediated upregulation of pro-inflammatory mediators' expression such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-a (TNF-α) in both BV2 microglia and primary microglia cells...
August 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28821568/lrrk2-promotes-the-activation-of-nlrc4-inflammasome-during-salmonella-typhimurium-infection
#16
Weiwei Liu, Xia'nan Liu, Yu Li, Junjie Zhao, Zhenshan Liu, Zhuqin Hu, Ying Wang, Yufeng Yao, Aaron W Miller, Bing Su, Mark R Cookson, Xiaoxia Li, Zizhen Kang
Although genetic polymorphisms in the LRRK2 gene are associated with a variety of diseases, the physiological function of LRRK2 remains poorly understood. In this study, we report a crucial role for LRRK2 in the activation of the NLRC4 inflammasome during host defense against Salmonella enteric serovar Typhimurium infection. LRRK2 deficiency reduced caspase-1 activation and IL-1β secretion in response to NLRC4 inflammasome activators in macrophages. Lrrk2(-/-) mice exhibited impaired clearance of pathogens after acute S...
October 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28750357/protective-effects-of-wedelolactone-on-dextran-sodium-sulfate-induced-murine-colitis-partly-through-inhibiting-the-nlrp3-inflammasome-activation-via-ampk-signaling
#17
Wencheng Wei, Meiling Ding, Kai Zhou, Haifeng Xie, Mian Zhang, Chaofeng Zhang
It has been reported that the ethanol extract of Wedelia chinensis attenuates murine colitis. Wedelolactone (WEL), a coumestane-type compound with many pharmacological activities, was isolated from W. chinensis. The present study aims to investigate the beneficial effects and underlying mechanisms of WEL on ulcerative colitis. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of WEL (50mg/kg) significantly attenuated pathological colonic damage and inhibited inflammatory infiltration, myeloperoxidase and alkaline phosphatase activities through MAPKs and NF-κB signaling pathways, while activating AMPK in colons treated with DSS...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28750089/a-synthetic-cationic-antimicrobial-peptide-inhibits-inflammatory-response-and-the-nlrp3-inflammasome-by-neutralizing-lps-and-atp
#18
Lan-Hui Li, Tz-Chuen Ju, Chih-Yu Hsieh, Wei-Chih Dong, Wan-Tze Chen, Kuo-Feng Hua, Wei-Jung Chen
Antimicrobial peptides (AMPs) are one of the most important defense mechanisms against bacterial infections in insects, plants, non-mammalian vertebrates, and mammals. In the present study, a class of synthetic AMPs was evaluated for anti-inflammatory activity. One cationic AMP, GW-A2, demonstrated the ability to inhibit the expression levels of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-activated macrophages...
2017: PloS One
https://www.readbyqxmd.com/read/28732510/protective-and-therapeutic-role-of-2-carba-cyclic-phosphatidic-acid-in-demyelinating-disease
#19
Shinji Yamamoto, Kota Yamashina, Masaki Ishikawa, Mari Gotoh, Sosuke Yagishita, Kensuke Iwasa, Kei Maruyama, Kimiko Murakami-Murofushi, Keisuke Yoshikawa
BACKGROUND: Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We reported earlier that cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death...
July 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28716882/protein-kinase-d-at-the-golgi-controls-nlrp3-inflammasome-activation
#20
Zhirong Zhang, Gergö Meszaros, Wan-Ting He, Yanfang Xu, Helena de Fatima Magliarelli, Laurent Mailly, Michael Mihlan, Yansheng Liu, Marta Puig Gámez, Alexander Goginashvili, Adrien Pasquier, Olga Bielska, Bénédicte Neven, Pierre Quartier, Rudolf Aebersold, Thomas F Baumert, Philippe Georgel, Jiahuai Han, Romeo Ricci
The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated by MAM-derived effectors. Here, we show that in response to inflammasome activators, MAMs localize adjacent to Golgi membranes...
September 4, 2017: Journal of Experimental Medicine
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