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Inflammasome phosphorylation

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https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#1
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...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28928791/wu-mei-wan-reduces-insulin-resistance-via-inhibition-of-nlrp3-inflammasome-activation-in-hepg2-cells
#2
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
#3
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
#4
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
#5
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...
January 1, 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/28843178/esculentoside-a-exerts-anti-inflammatory-activity-in-microglial-cells
#6
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
#7
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...
August 18, 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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28709622/genipin-protects-d-galactosamine-and-lipopolysaccharide-induced-hepatic-injury-through-suppression-of-the-necroptosis-mediated-inflammasome-signaling
#12
Min-Jong Seo, Jeong-Min Hong, Seok-Joo Kim, Sun-Mee Lee
Acute liver failure (ALF) is a life-threatening syndrome resulting from massive inflammation and hepatocyte death. Necroptosis, a programmed cell death controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, has been shown to play an important role in regulating inflammation via crosstalk between other intracellular signaling. The inflammasome is a major intracellular multiprotein that induces inflammatory responses by mediating immune cell infiltration, thus potentiating injury. Genipin, a major active compound of the gardenia fruit, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties...
July 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28671960/stress-fibers-autophagy-and-necrosis-by-persistent-exposure-to-pm2-5-from-biomass-combustion
#13
Regina Dornhof, Christoph Maschowski, Anastasiya Osipova, Reto Gieré, Maximilian Seidl, Irmgard Merfort, Matjaz Humar
Fine particulate matter (PM2.5) can adversely affect human health. Emissions from residential energy sources have the largest impact on premature mortality globally, but their pathological and molecular implications on cellular physiology are still elusive. In the present study potential molecular consequences were investigated during long-term exposure of human bronchial epithelial BEAS-2B cells to PM2.5, collected from a biomass power plant. Initially, we observed that PM2.5 did not affect cellular survival or proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28652704/rhein-attenuates-inflammation-through-inhibition-of-nf-%C3%AE%C2%BAb-and-nalp3-inflammasome-in-vivo-and-in-vitro
#14
Hui Ge, Hao Tang, Yanbing Liang, Jingguo Wu, Qing Yang, Lijin Zeng, Zhongfu Ma
Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28642632/mcl-plays-an-anti-inflammatory-role-in-mycobacterium-tuberculosis-induced-immune-response-by-inhibiting-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#15
Qingwen Zhang, Xinru Jiang, Weigang He, Kailin Wei, Jinxia Sun, Xiangyang Qin, Yuejuan Zheng, Xin Jiang
Mycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634425/a-transcriptional-regulatory-role-for-the-membrane-type-1-matrix-metalloproteinase-in-carcinogen-induced-inflammasome-gene-expression
#16
Samuel Sheehy, Borhane Annabi
Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28598074/-sodium-ferulate-attenuates-oxidative-stressvia-suppressing-nalp3-inflammasome-and-erk-signal-pathway
#17
Xiao-Lin Wei, Min Xie, Gao-Yan He
OBJECTIVES: Study the gene and protein expression of NACHT-PYD-containing protein 3 (NALP3) inflammasome and extracellular regulated protein kinase (ERK), the intervention effects of sodium ferulate (SF) in human lung epithelial cells A549 under oxidative stress, and to investigate the possible mechanism. METHODS: Human lung epithelial cells A549 cultured in vitro were divided into 6 groups, including control group,H₂O₂(200 umol/L) group, SF group (400 ug/mL), caspase-1 blockers (Z-VAD) group (Z-VAD 20 umol/L+H₂O₂200 umol/L), ERK blockers (PD98059) group (PD98059 50 umol/L+H₂O₂ 200 umol/L), and SF+H₂O₂ group (SF 400 ug/mL+H₂O₂ 200 umol/L)...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28583762/puerarin-inhibits-amyloid-%C3%AE-induced-nlrp3-inflammasome-activation-in-retinal-pigment-epithelial-cells-via-suppressing-ros-dependent-oxidative-and-endoplasmic-reticulum-stresses
#18
Ke Wang, Xue Zhu, Kai Zhang, Yong Yao, Miao Zhuang, Chengye Tan, Fanfan Zhou, Ling Zhu
Amyloid β (Aβ) is a critical stimulator that promotes the progression of age-related macular degeneration (AMD). NLRP3 inflammasome activation induced by Aβ is estimated to be responsible for retinal pigment epithelium (RPE) dysfunction in such disease. Puerarin, one of the major active constituents of Kudzu root, has been widely used in the clinical treatment of AMD in China for decades; however, the detailed molecular mechanism remains far from clear. In this study, we investigated the protective effect and underlying mechanism of puerarin against Aβ1-40-induced NLRP3 inflammasome activation in LPS-primed ARPE-19 cells...
August 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28582770/the-protective-effect-of-epimedii-folium-and-curculiginis-rhizoma-on-alzheimer-s-disease-by-the-inhibitions-of-nf-%C3%AE%C2%BAb-mapk-pathway-and-nlrp3-inflammasome
#19
Zhou Lan, Guangjing Xie, Meng Wei, Ping Wang, Lvyi Chen
The purpose of the current study was to explore the effects of the water extracts of Epimedii Folium and Curculiginis Rhizoma (EX) on Aβ-induced Alzheimer's disease. Aβ1-42 was stereotaxically injected bilaterally into the dorsal hippocampus, and then the rats were orally received EX at the doses of 2 g/kg and 6 g/kg for 30 days. Behavior was monitored through Morris water maze test. The neuroprotective effect of EX were examined with methods of histochemistry and biochemistry. EX reduced the contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and cortex...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28579326/rip1-rip3-drp1-pathway-regulates-nlrp3-inflammasome-activation-following-subarachnoid-hemorrhage
#20
Keren Zhou, Ligen Shi, Zhen Wang, Jingyi Zhou, Anatol Manaenko, Cesar Reis, Sheng Chen, Jianmin Zhang
The NLRP3 inflammasome functions as a crucial component of the inflammatory response in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the activation of NLRP3 inflammasome has not been well elucidated. In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection...
September 2017: Experimental Neurology
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