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Inflammasome phosphorylation

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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
#1
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
#2
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
#3
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
#4
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...
June 2, 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
#5
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...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28579326/rip1-rip3-drp1-pathway-regulates-nlrp3-inflammasome-activation-following-subarachnoid-hemorrhage
#6
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...
June 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28526339/magnesium-isoglycyrrhizinate-blocks-fructose-induced-hepatic-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-and-lipid-metabolism-disorder
#7
Xiao-Juan Zhao, Yan-Zi Yang, Yan-Jing Zheng, Shan-Chun Wang, Hong-Mei Gu, Ying Pan, Shui-Juan Wang, Hong-Jiang Xu, Ling-Dong Kong
Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels...
May 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28499186/effect-of-betaine-on-hepatic-insulin-resistance-through-foxo1-induced-nlrp3-inflammasome
#8
Dae Hyun Kim, Seong Min Kim, Bonggi Lee, Eun Kyeong Lee, Ki Wung Chung, Kyoung Mi Moon, Hye Jin An, Kyung Mok Kim, Byung Pal Yu, Hae Young Chung
In the present study, we attempted to elucidate whether molecular modulation of inflammation by betaine through the forkhead box O1 (FOXO1)-induced NLRP3 inflammasome improves insulin resistance. Betaine is a major water-soluble component of Lycium chinense. It mainly functions as an oxidative metabolite of choline by suppressing superoxide-induced free radicals by donating methyl groups. The FOXO1 transcription factor regulates various genes involved in cellular metabolic processes related to cell death as well as oxidative stress responses through binding to the thioredoxin-interacting protein (TXNIP)...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28473584/anti-inflammatory-effect-of-il-10-mediated-by-metabolic-reprogramming-of-macrophages
#9
W K Eddie Ip, Namiko Hoshi, Dror S Shouval, Scott Snapper, Ruslan Medzhitov
Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4...
May 5, 2017: Science
https://www.readbyqxmd.com/read/28473446/human-plasma-thioredoxin-80-increases-with-age-and-in-apoe-mice-induces-inflammation-angiogenesis-and-atherosclerosis
#10
Dominique Couchie, Boris Vaisman, Amna Abderrazak, Dler Faieeq Darweesh Mahmood, Magda M Hamza, Fanny Canesi, Vimala Diderot, Khadija El Hadri, Anne E Nègre-Salvayre, Aurélie Le Page, Tamas Fulop, Alan T Remaley, Mustapha Rouis
Background -Thioredoxin-1 (TRX1), a ubiquitous 12 kDa protein, exerts anti-oxidant and anti-inflammatory effects. In contrast, the truncated form, called TRX80, produced by macrophages induces up-regulation of pro-inflammatory cytokines. TRX80 also promotes the differentiation of mouse peritoneal and human macrophages toward a pro-inflammatory M1 phenotype. Methods -TRX1 and TRX80 plasma levels were determined using specific ELISA. ADAM-17 and ADAM-10 activities were measured using respectively SensoLyte® 520 ADAM10 Activity Assay Kit *Fluorimetric* and InnoZyme™ TACE Activity Kit...
May 4, 2017: Circulation
https://www.readbyqxmd.com/read/28465465/nlrp3-inflammasome-assembly-is-regulated-by-phosphorylation-of-the-pyrin-domain
#11
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)...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28462524/ripk3-driven-cell-death-during-virus-infections
#12
REVIEW
Jason W Upton, Maria Shubina, Siddharth Balachandran
The programmed self-destruction of infected cells is a powerful antimicrobial strategy in metazoans. For decades, apoptosis represented the dominant mechanism by which the virus-infected cell was thought to undergo programmed cell death. More recently, however, new mechanisms of cell death have been described that are also key to host defense. One such mechanism in vertebrates is programmed necrosis, or "necroptosis", driven by receptor-interacting protein kinase 3 (RIPK3). Once activated by innate immune stimuli, including virus infections, RIPK3 phosphorylates the mixed lineage kinase domain-like protein (MLKL), which then disrupts cellular membranes to effect necroptosis...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#13
Thomas Ondet, Béatrice Muscatelli-Groux, Cédric Coulouarn, Sacha Robert, Thomas Gicquel, Aude Bodin, Vincent Lagente, Jean-Alexis Grimaud
Toll like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the three-dimensional structure of pathogen associated molecules and are thus useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides (LPS) and monosodium urate (MSU) crystals in the activation of the TLR and Nod Like Receptors (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NLRP3 and TLR4, both of which are components of inflammasome complexes involved in the activation of IL-1β, were not expressed in keratinocytes...
April 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28415686/chikusetsu-saponin-iva-ameliorates-high-fat-diet-induced-inflammation-in-adipose-tissue-of-mice-through-inhibition-of-nlrp3-inflammasome-activation-and-nf-%C3%AE%C2%BAb-signaling
#14
Chengfu Yuan, Chaoqi Liu, Ting Wang, Yumin He, Zhiyong Zhou, Yaoyan Dun, Haixia Zhao, Dongming Ren, Junjie Wang, Changcheng Zhang, Ding Yuan
Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28349253/mangiferin-suppresses-endoplasmic-reticulum-stress-in-perivascular-adipose-tissue-and-prevents-insulin-resistance-in-the-endothelium
#15
Xiaoshan Xu, Yupeng Chen, Junna Song, Fangjie Hou, Xuelian Ma, Baolin Liu, Fang Huang
PURPOSE: Mangiferin is a naturally occurring glucosylxanthone with beneficial effects on glucose and lipid homeostasis. This study investigates the potential therapeutic effect of Mangiferin in perivascular adipose tissue (PVAT) and whether it contributes to regulating insulin action in the endothelium. METHODS: Palmitate challenge evoked ROS-associated endoplasmic reticulum stress (ER stress) and NLRP3 inflammasome activation in PVAT. The conditioned medium from PA-stimulated PVAT was prepared to induce endothelial insulin resistance, and improved endothelium-dependent vasodilation in response to insulin was detected in vitro and in vivo...
March 27, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#16
Yue Wang, Zhihua Han, Yuqi Fan, Junfeng Zhang, Kan Chen, Lin Gao, Huasu Zeng, Jiatian Cao, Changqian Wang
BACKGROUND/AIMS: MicroRNA-9 (miR-9) is involved in inflammatory reaction in atherosclerosis; however, its function and regulatory mechanisms remain unclear. We aimed to uncover the exact roles of miR-9 and downstream signaling pathways using in vitro human atherosclerosis models. METHODS: We used oxidized low-density lipoprotein (oxLDL)-stimulated human THP-1 derived macrophages, oxLDL-stimulated human primary peripheral blood monocytes and lipopolysaccharides (LPS) or Alum-stimulated human THP-1 derived macrophages as in vitro atherosclerosis inflammation models...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28315674/dichotomy-between-receptor-interacting-protein-1-and-receptor-interacting-protein-3-mediated-necroptosis-in-experimental-pancreatitis
#17
Jianghong Wu, Tunike Mulatibieke, Jianbo Ni, Xiao Han, Bin Li, Yue Zeng, Rong Wan, Xingpeng Wang, Guoyong Hu
Pancreatic acinar cell necrosis and inflammatory responses are two key pathologic processes in acute pancreatitis (AP), which determines the severity and outcome of the disease. Recent studies suggest that necroptosis, a programed form of necrosis, is involved in the pathogenesis of AP, but the underlying mechanisms remain unknown. We investigated the expression of necrosome components, including receptor-interacting protein (RIP) 1, RIP3, and mixed lineage kinase domain-like (MLKL), and the molecular mechanisms in pancreatitis-associated necroptosis...
March 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#18
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
June 2017: Immunologic Research
https://www.readbyqxmd.com/read/28285192/xanthohumol-ameliorates-lipopolysaccharide-lps-induced-acute-lung-injury-via-induction-of-ampk-gsk3%C3%AE-nrf2-signal-axis
#19
Hongming Lv, Qinmei Liu, Zhongmei Wen, Haihua Feng, Xuming Deng, Xinxin Ci
Abundant natural flavonoids can induce nuclear factor-erythroid 2 related factor 2 (Nrf2) and/or AMP-activated protein kinase (AMPK) activation, which play crucial roles in the amelioration of various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Xanthohumol (Xn), a principal prenylflavonoid, possesses anti-inflammation and anti-oxidant activities. However, whether Xn could protect from LPS-induced ALI through inducing AMPK/Nrf2 activation and its downstream signals, are still poorly elucidated...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28279687/airborne-particulate-matter-in-vitro-exposure-induces-cytoskeleton-remodeling-through-activation-of-the-rock-mypt1-mlc-pathway-in-a549-epithelial-lung-cells
#20
Yolanda I Chirino, Claudia María García-Cuellar, Carlos García-García, Ernesto Soto-Reyes, Álvaro Román Osornio-Vargas, Luis A Herrera, Alejandro López-Saavedra, Javier Miranda, Raúl Quintana-Belmares, Irma Rosas Pérez, Yesennia Sánchez-Pérez
Airborne particulate matter with an aerodynamic diameter ≤10μm (PM10) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM10 exposure in A549 lung epithelial cells...
April 15, 2017: Toxicology Letters
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