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Inflammasome phosphorylation

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https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#1
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...
March 27, 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
#2
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
#3
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...
March 13, 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
#4
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...
March 2, 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
#5
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...
March 6, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28253220/fat-mass-and-obesity-associated-protein-attenuates-lipid-accumulation-in-macrophage-foam-cells-and-alleviates-atherosclerosis-in-apolipoprotein-e-deficient-mice
#6
Chunfen Mo, Ming Yang, Xiaojuan Han, Junhong Li, Guangping Gao, Haoran Tai, Ning Huang, Hengyi Xiao
OBJECTIVE: Genome-wide association studies have linked variants of fat mass and obesity-associated protein (FTO) to obesity. However, the molecular function of FTO remains unclear. In this study, we sought to investigate the potential effects of FTO in modulating cholesterol deposition in macrophage foam cells, as well as whether FTO exerts antiatherosclerotic properties in apolipoprotein E-deficient mice. METHOD AND RESULTS: We transfected RAW264.7 cells with plasmids encoding a wild-type or mutant FTO gene (I367F)...
April 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28238167/effects-of-cox1-2-5-lox-blockade-in-alzheimer-transgenic-3xtg-ad-mice
#7
Alessandra Bitto, Daniela Giuliani, Giovanni Pallio, Natasha Irrera, Eleonora Vandini, Fabrizio Canalini, Davide Zaffe, Alessandra Ottani, Letteria Minutoli, Mariagrazia Rinaldi, Salvatore Guarini, Francesco Squadrito, Domenica Altavilla
OBJECTIVE AND DESIGN: Alzheimer's disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice. SUBJECTS: Mice were 3 months at the beginning of the study. TREATMENT: Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip)...
February 25, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28219839/sinigrin-inhibits-production-of-inflammatory-mediators-by-suppressing-nf-%C3%AE%C2%BAb-mapk-pathways-or-nlrp3-inflammasome-activation-in-macrophages
#8
Hee-Weon Lee, Chung Gi Lee, Dong-Kwon Rhee, Sung Hee Um, Sukneung Pyo
Sinigrin (2-propenyl glucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health. This study investigated the effect of sinigrin on macrophage function, including the activity of Nod-like receptor protein 3 (NLRP3) inflammasome. In a concentration-dependent manner, sinigrin inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production and the expression of COX-2 and prostaglandin E2 (PGE2) in RAW 264...
February 17, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28217966/pathogenesis-of-diffuse-alveolar-hemorrhage-in-murine-lupus
#9
Haoyang Zhuang, Shuhong Han, Pui Y Lee, Ravil Khaybullin, Stepan Shumyak, Li Lu, Amina Chatha, Anan Afaneh, Yuan Zhang, Chao Xie, Dina Nacionales, Lyle Moldawer, Xin Qi, Li-Jun Yang, Westley H Reeves
OBJECTIVE: Diffuse alveolar hemorrhage (DAH) in lupus patients is >50% fatal. The cause is unknown. The pathogenesis of DAH in C57BL/6 mice with pristane-induced lupus, a model of human lupus-associated DAH, was examined. METHODS: Clinical/pathological and immunological manifestations DAH in pristane-lupus were compared with human DAH. Tissue distribution of pristane was examined by mass spectrometry. Cell types responsible for disease were determined by in vivo depletion using clodronate liposomes (CloLip) and anti-neutrophil monoclonal antibodies (GR1)...
February 19, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28188924/daphnetin-mediated-nrf2-antioxidant-signaling-pathways-ameliorate-tert-butyl-hydroperoxide-t-bhp-induced-mitochondrial-dysfunction-and-cell-death
#10
Hongming Lv, Qinmei Liu, Junfeng Zhou, Guangyun Tan, Xuming Deng, Xinxin Ci
Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio...
February 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28160545/impact-of-resistance-training-on-the-autophagy-inflammation-apoptosis-crosstalk-in-elderly-subjects
#11
Yubisay Mejías-Peña, Brisamar Estébanez, Paula Rodriguez-Miguelez, Rodrigo Fernandez-Gonzalo, Mar Almar, José A de Paz, Javier González-Gallego, María J Cuevas
Aging is associated with a decline in autophagy and a state of low-grade inflammation which further affects apoptosis and autophagy. Importantly, these alterations could reverse with regular physical activity. This study assessed the effects of a resistance exercise training program on autophagy, NLRP3 inflammasome, and apoptosis in peripheral blood mononuclear cells (PBMCs) from old subjects. Twenty-six healthy women and men (age, 69.6±1.5 yr) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week resistance training program, while CG followed their daily routines...
February 2, 2017: Aging
https://www.readbyqxmd.com/read/28152446/therapeutic-efficacy-of-carboxyamidotriazole-on-2-4-6-trinitrobenzene-sulfonic-acid-induced-colitis-model-is-associated-with-the-inhibition-of-nlrp3-inflammasome-and-nf-%C3%AE%C2%BAb-activation
#12
Xiaowan Du, Wei Chen, Yufeng Wang, Chen Chen, Lei Guo, Rui Ju, Juan Li, Dechang Zhang, Lei Zhu, Caiying Ye
Excess proinflammatory cytokines owing to the activation of NF-κB and NLRP3 inflammasome play the key role in inflammatory bowel disease (IBD). Previously, we reported the anti-inflammatory activity of carboxyamidotriazole (CAI) resulting from decreasing cytokines. Therefore, we investigated the therapeutic effects of CAI in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat colitis and the involvement of CAI action with NLRP3 inflammasome and NF-κB pathway. CAI was orally administered to TNBS-induced colitis rat...
January 30, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28132925/combined-nadph-and-the-nox-inhibitor-apocynin-provides-greater-anti-inflammatory-and-neuroprotective-effects-in-a-mouse-model-of-stroke
#13
Yuan-Yuan Qin, Mei Li, Xing Feng, Jian Wang, Lijuan Cao, Xi-Kui Shen, Jieyu Chen, Meiling Sun, Rui Sheng, Feng Han, Zheng-Hong Qin
Our previous study has reported that the pentose phosphate pathway product nicotinamide adenine dinucleotide phosphate (NADPH) protected neurons against ischemia/reperfusion-induced brain injury. NADPH can either act as a co-enzyme to produce GSH or a substrate of NADPH oxidase (NOX) to generate ROS. This study was designed to elucidate the effects of co-treatment with NADPH and NOX inhibitor apocynin on ischemia/reperfusion-induced brain inflammation and neuronal injury. The results showed that both NADPH and apocynin markedly attenuated ischemia/reperfusion-induced increases in the levels of NOX2, NOX4 and ROS...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28125719/toxoplasma-gondii-gra7-targeted-asc-and-pld1-promote-antibacterial-host-defense-via-pkc%C3%AE
#14
Hyun-Jung Koh, Ye-Ram Kim, Jae-Sung Kim, Jin-Seung Yun, Kiseok Jang, Chul-Su Yang
Tuberculosis is a global health problem and at least one-third of the world's population is infected with Mycobacterium tuberculosis (MTB). MTB is a successful pathogen that enhances its own intracellular survival by inhibiting inflammation and arresting phago-lysosomal fusion. We previously demonstrated that Toxoplasma gondii (T. gondii) dense granule antigen (GRA) 7 interacts with TNF receptor-associated factor 6 via Myeloid differentiation primary response gene 88, enabling innate immune responses in macrophages...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28115215/damaging-heterozygous-mutations-in-nfkb1-lead-to-diverse-immunologic-phenotypes
#15
Meri Kaustio, Emma Haapaniemi, Helka Göös, Timo Hautala, Giljun Park, Jaana Syrjänen, Elisabet Einarsdottir, Biswajyoti Sahu, Sanna Kilpinen, Samuli Rounioja, Christopher L Fogarty, Virpi Glumoff, Petri Kulmala, Shintaro Katayama, Fitsum Tamene, Luca Trotta, Ekaterina Morgunova, Kaarel Krjutškov, Katariina Nurmi, Kari Eklund, Anssi Lagerstedt, Merja Helminen, Timi Martelius, Satu Mustjoki, Jussi Taipale, Janna Saarela, Juha Kere, Markku Varjosalo, Mikko Seppänen
BACKGROUND: The nuclear factor κ light-chain enhancer of activated B cells (NF-κB) signaling pathway is a key regulator of immune responses. Accordingly, mutations in several NF-κB pathway genes cause immunodeficiency. OBJECTIVE: We sought to identify the cause of disease in 3 unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation. METHODS: We applied genetic linkage analysis and next-generation sequencing and functional analyses of NFKB1 and its mutated alleles...
January 21, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28100477/inability-to-replete-white-adipose-tissue-during-the-recovery-phase-of-sepsis-is-associated-with-increased-autophagy-apoptosis-and-proteasome-activity
#16
Kristen T Crowell, David I Soybel, Charles H Lang
Adipose tissue is an important energy depot and endocrine organ, and the degree of adiposity impacts the host response to infection. However, little is known regarding the mechanisms by which white adipose tissue (WAT) is lost acutely and then restored after resolution of sepsis. Therefore, signaling pathways governing protein synthesis, autophagy, apoptosis and the ubiquitin-proteasome were investigated to identify potential mechanisms mediating the acute (24 h) loss of WAT after cecal ligation and puncture (CLP) as well as the failure to replenish WAT during recovery (day 10)...
January 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28097088/icariin-ameliorates-iga-nephropathy-by-inhibition-of-nuclear-factor-kappa-b-nlrp3-pathway
#17
Lei Zhang, Xing-Zhi Wang, Yu-Shu Li, Lei Zhang, Li-Rong Hao
Immunoglobulin A nephropathy (IgAN) is the most frequent form of glomerulonephritis, which is characterized by glomerular proliferation and renal inflammation. Icariin is a flavonoid from the Chinese herb Epimedium, and its anti-inflammatory effect has been reported. This study aimed to investigate the effects of icariin on the renal damage in IgAN rats and the mechanisms behind these effects. IgAN model was established in Sprague-Dawley rats by oral and intravenous immunization with bovine gamma-globulin for 12 weeks, and rats were treated with icariin from 12 to 18 weeks...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28096356/active-mlkl-triggers-the-nlrp3-inflammasome-in-a-cell-intrinsic-manner
#18
Stephanie A Conos, Kaiwen W Chen, Dominic De Nardo, Hideki Hara, Lachlan Whitehead, Gabriel Núñez, Seth L Masters, James M Murphy, Kate Schroder, David L Vaux, Kate E Lawlor, Lisa M Lindqvist, James E Vince
Necroptosis is a physiological cell suicide mechanism initiated by receptor-interacting protein kinase-3 (RIPK3) phosphorylation of mixed-lineage kinase domain-like protein (MLKL), which results in disruption of the plasma membrane. Necroptotic cell lysis, and resultant release of proinflammatory mediators, is thought to cause inflammation in necroptotic disease models. However, we previously showed that MLKL signaling can also promote inflammation by activating the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome to recruit the adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and trigger caspase-1 processing of the proinflammatory cytokine IL-1β...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096316/bay-11-7082-inhibits-the-nf-kb-and-nlrp3-inflammasome-pathways-and-protects-against-imq-induced-psoriasis
#19
Natasha Irrera, Mario Vaccaro, Alessandra Bitto, Giovanni Pallio, Gabriele Pizzino, Maria Lentini, Vincenzo Arcoraci, Letteria Minutoli, Michele Scuruchi, Giuseppina Cutroneo, Giuseppe Pio Anastasi, Roberta Ettari, Francesco Squadrito, Domenica Altavilla
BAY 11-7082 antagonizes I-κB kinase-β preventing nuclear translocation of NF-κB; it also inhibits NLRP3 inflammasome activation.NF-κB is involved in psoriasis, while the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod cream (IMQ; 62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knock-out mice for 7 consecutive days. Sham psoriasis animals were challenged with vaseline cream...
January 17, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28072760/pentoxifylline-inhibits-tlr-and-inflammasome-mediated-in-vitro-inflammatory-cytokine-production-in-human-blood-with-greater-efficacy-and-potency-in-newborns
#20
Esther M Speer, David J Dowling, Lukasz S Ozog, Jianjin Xu, Jie Yang, Geetika Kennady, Ofer Levy
BACKGROUND: Toll-like receptor (TLR)-mediated inflammation may contribute to neonatal sepsis, for which pentoxifylline (PTX), a phosphodiesterase inhibitor that raises intracellular cAMP, is a candidate adjunctive therapy. We characterized the anti-inflammatory effects of PTX towards TLR-mediated production of inflammatory (TNF, IL-1ß) and pro-resolution (IL-6, IL- 10) cytokines in human newborn and adult blood. METHODS: Newborn cord and adult blood were treated with PTX (50 - 400 μM) before, during or after stimulation with LPS (TLR4 agonist), R848 (TLR7/8 agonist) or LPS/ATP (inflammasome activation)...
January 10, 2017: Pediatric Research
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