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https://www.readbyqxmd.com/read/28109896/the-nlrp3-inflammasome-modulates-sleep-and-nrem-sleep-delta-power-induced-by-spontaneous-wakefulness-sleep-deprivation-and-lipopolysaccharide
#1
Mark R Zielinski, Dmitry Gerashchenko, Svetlana A Karpova, Varun Konanki, Robert W McCarley, Fayyaz S Sutterwala, Robert E Strecker, Radhika Basheer
Both sleep loss and pathogens can enhance brain inflammation, sleep, and sleep intensity as indicated by electroencephalogram delta (δ) power. The pro-inflammatory cytokine interleukin-1 beta (IL-1β) is increased in the cortex after sleep deprivation (SD) and in response to the Gram-negative bacterial cell-wall component lipopolysaccharide (LPS), although the exact mechanisms governing these effects are unknown. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome protein complex forms in response to changes in the local environment and, in turn, activates caspase-1 to convert IL-1β into its active form...
January 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28107794/a-study-on-the-gc-ms-analysis-of-bioactive-components-and-pancreato-protective-effect-of-methanolic-extract-of-brassica-oleracea-l-var-botrytis
#2
Sadanandan Rajapriya, Arumugam Geetha, Kavasseri Ganesan Kripa
The ever-increasing problem of pancreatitis due to alcohol abuse demands evaluation of novel drugs of plant origin. This study explores the therapeutic effects of the methanolic extract of Brassica oleraceae (MEBO) on ethanol and cerulein induced pancreatitis in rats. The MEBO was subjected to GC-MS and HPLC analysis. Male albino Wistar rats were divided into various groups, fed with alcohol (36% of total calories for 5 weeks) and cerulein (20 μg/kg b.wt i.p, weekly thrice for last three weeks) with or without MEBO (40 mg/kg b...
January 20, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28102121/inflammasomes-in-myeloid-cells-warriors-within
#3
Sushmita Jha, W June Brickey, Jenny Pan-Yun Ting
The inflammasome is a large multimeric protein complex comprising an effector protein that demonstrates specificity for a variety of activators or ligands; an adaptor molecule; and procaspase-1, which is converted to caspase-1 upon inflammasome activation. Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice, and several have been genetically linked to human diseases...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28102119/glutathione-and-glutathione-transferase-omega-1-as-key-posttranslational-regulators-in-macrophages
#4
Mark M Hughes, Anne F McGettrick, Luke A J O'Neill
Macrophage activation during phagocytosis or by pattern recognition receptors, such as Toll-like receptor 4, leads to the accumulation of reactive oxygen species (ROS). ROS act as a microbicidal defense mechanism, promoting clearance of infection, allowing for resolution of inflammation. Overproduction of ROS, however, overwhelms our cellular antioxidant defense system, promoting oxidation of protein machinery, leading to macrophage dysregulation and pathophysiology of chronic inflammatory conditions, such as atherosclerosis...
January 2017: Microbiology Spectrum
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
#5
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/28096454/mitochondrial-function-is-required-for-extracellular-atp-induced-nlrp3-inflammasome-activation
#6
Daichi Sadatomi, Kazutaka Nakashioya, Sayaka Mamiya, Shino Honda, Yuka Kameyama, Yasuo Yamamura, Susumu Tanimura, Kohsuke Takeda
The NLRP3 inflammasome plays a critical role in the processing and release of inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. Accumulating evidence suggests that mitochondria are common mediators of NLRP3 inflammasome activation induced by a wide range of inflammatory stimuli; however, the precise role of mitochondria is still not fully understood. Here, we show that mitochondrial function is required for extracellular ATP-induced NLRP3 inflammasome activation. Extracellular ATP induced the loss of mitochondrial membrane potential and mitochondrial fragmentation in a different manner than other stimuli in primary mouse macrophages...
January 17, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28096356/active-mlkl-triggers-the-nlrp3-inflammasome-in-a-cell-intrinsic-manner
#7
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...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095655/production-of-il-1%C3%AE-and-inflammasome-with-up-regulated-expressions-of-nod-like-receptor-related-genes-in-toxoplasma-gondii-infected-thp-1-macrophages
#8
Jia-Qi Chu, Ge Shi, Yi-Ming Fan, In-Wook Choi, Guang-Ho Cha, Yu Zhou, Young-Ha Lee, Juan-Hua Quan
Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of pro-IL-1β. To elucidate the role of inflammasome components in T. gondii-infected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine IL-1β secretion...
December 2016: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28093447/inflammasomes-and-cancer
#9
Rajendra Karki, Si Ming Man, Thirumala-Devi Kanneganti
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28089560/critical-role-of-p2x7-receptors-in-the-neuroinflammation-and-cognitive-dysfunction-after-surgery
#10
Bin Zheng, Renchun Lai, Jun Li, Zhiyi Zuo
Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane...
January 9, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28087670/plant-lectins-activate-the-nlrp3-inflammasome-to-promote-inflammatory-disorders
#11
Tao Gong, Xiaqiong Wang, Yanqing Yang, Yiqing Yan, Chenggong Yu, Rongbin Zhou, Wei Jiang
Plant-derived dietary lectins have been reported to be involved in the pathogenesis of several inflammatory diseases, including inflammatory bowel disease, diabetes, rheumatoid arthritis, and celiac disease, but little is known about the molecular mechanisms underlying lectin-induced inflammation. In this study, we showed that plant lectins can induce caspase-1 activation and IL-1β secretion via the NLRP3 inflammasome. Lectins were internalized and subsequently escaped from the lysosome and then translocated to the endoplasmic reticulum...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087651/frontline-science-multiple-cathepsins-promote-inflammasome-independent-particle-induced-cell-death-during-nlrp3-dependent-il-1%C3%AE-activation
#12
Gregory M Orlowski, Shruti Sharma, Jeff D Colbert, Matthew Bogyo, Stephanie A Robertson, Hiroshi Kataoka, Francis K Chan, Kenneth L Rock
Sterile particles cause several chronic, inflammatory diseases, characterized by repeating cycles of particle phagocytosis and inflammatory cell death. Recent studies have proposed that these processes are driven by the NLRP3 inflammasome, a platform activated by phagocytosed particles, which controls both caspase-1-dependent cell death (pyroptosis) and mature IL-1β secretion. After phagocytosis, particles can disrupt lysosomes, and inhibitor studies have suggested that the resulting release of a lysosomal protease-cathepsin B-into the cytosol somehow activates NLRP3...
January 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28081233/differences-in-inflammatory-response-induced-by-two-representatives-of-clades-of-the-pandemic-st258-klebsiella-pneumoniae-clonal-lineage-producing-kpc-type-carbapenemases
#13
Giuseppe Castronovo, Ann Maria Clemente, Alberto Antonelli, Marco Maria D'Andrea, Michele Tanturli, Eloisa Perissi, Sara Paccosi, Astrid Parenti, Federico Cozzolino, Gian Maria Rossolini, Maria Gabriella Torcia
ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28077335/omega-3-fatty-acids-regulate-nlrp3-inflammasome-activation-and-prevent-behavior-deficits-after-traumatic-brain-injury
#14
Chao Lin, Honglu Chao, Zheng Li, Xiupeng Xu, Yinlong Liu, Zhongyuan Bao, Lijun Hou, Yan Liu, Xiaoming Wang, Yongping You, Ning Liu, Jing Ji
Omega-3 fatty acids (ω-3 FAs) attenuate inflammation and improve neurological outcome in response to traumatic brain injury (TBI), but the specific anti-inflammatory mechanisms remain to be elucidated. Here we found that NLRP3 inflammasome and subsequent pro-inflammatory cytokines were activated in human brains after TBI. Rats treated with ω-3 FAs had significantly less TBI-induced caspase-1 cleavage and IL-1β secretion than those with vehicle. G protein-coupled receptor 40 (GPR40) was observed to be involved in this anti-inflammation...
January 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28073832/reperfusion-therapy-with-recombinant-human-relaxin-2-serelaxin-attenuates-myocardial-infarct-size-and-nlrp3-inflammasome-following-ischemia-reperfusion-injury-via-enos-dependent-mechanism
#15
Juan Valle Raleigh, Adolfo G Mauro, Teja Devarakonda, Carlo Marchetti, Jun He, Erica Kim, Scott Filippone, Anindita Das, Stefano Toldo, Antonio Abbate, Fadi N Salloum
AIMS: The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin-2, serelaxin, reduces myocardial infarct size and attenuates the subsequent NLRP3 inflammasome activation leading to further loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown. METHODS AND RESULTS: After baseline echocardiography, adult male wild-type C57BL or eNOS knockout mice underwent myocardial infarction (MI) by coronary artery ligation for 30 min followed by 24 h reperfusion...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28069553/targeting-inflammasome-by-the-inhibition-of-caspase-1-activity-using-capped-mesoporous-silica-nanoparticles
#16
Alba García-Fernández, Guillermo García-Laínez, María Luisa Ferrándiz, Elena Aznar, Félix Sancenón, María José Alcaraz, José Ramón Murguía, María D Marcos, Ramón Martínez-Máñez, Ana M Costero, Mar Orzáez
Acute inflammation is a protective response of the body to harmful stimuli, such as pathogens or damaged cells. However, dysregulated inflammation can cause secondary damage and could thus contribute to the pathophysiology of many diseases. Inflammasomes, the macromolecular complexes responsible for caspase-1 activation, have emerged as key regulators of immune and inflammatory responses. Therefore, modulation of inflammasome activity has become an important therapeutic approach. Here we describe the design of a smart nanodevice that takes advantage of the passive targeting of nanoparticles to macrophages and enhances the therapeutic effect of caspase-1 inhibitor VX-765 in vivo...
January 6, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28068647/berberine-an-isoquinoline-alkaloid-suppresses-txnip-mediated-nlrp3-inflammasome-activation-in-msu-crystal-stimulated-raw-264-7-macrophages-through-the-upregulation-of-nrf2-transcription-factor-and-alleviates-msu-crystal-induced-inflammation-in-rats
#17
Palani Dinesh, MahaboobKhan Rasool
The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch-like ECH-associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase-1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264...
January 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28065854/the-mechanism-of-nlrp3-inflammasome-initiation-trimerization-but-not-dimerization-of-the-nlrp3-pyrin-domain-induces-robust-activation-of-il-1%C3%AE
#18
Petra Sušjan, Samo Roškar, Iva Hafner-Bratkovič
NLRP3 inflammasome is a multiprotein platform for the activation of caspase-1. Despite the increasing number of reports linking NLRP3 inflammasome to a variety of diseases, the mechanism behind the NLRP3 activation remains elusive, especially in terms of the early stages which are critical to the NLRP3 inflammasome assembly. In the present study we aimed to determine the minimal oligomerization state required for the NLRP3 inflammasome activation. For this purpose, NLRP3 pyrin domain (NLRP3(PYD)) was fused to various dimerization and trimerization domains...
January 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28064010/vascular-endothelial-cells-senescence-is-associated-with-nod-like-receptor-family-pyrin-domain-containing-3-nlrp3-inflammasome-activation-via-reactive-oxygen-species-ros-thioredoxin-interacting-protein-txnip-pathway
#19
Yanlin Yin, Zhihui Zhou, Weiwei Liu, Qun Chang, Guanqun Sun, Yalei Dai
Endothelial dysfunction caused by endothelial cells senescence and chronic inflammation is tightly linked to the development of cardiovascular diseases. NLRP3 (NOD-like receptor family pyrin domain-containing3) inflammasome plays a central role in inflammatory response that is associated with diverse inflammatory diseases. This study explores the effects and possible mechanisms of NLRP3 inflammasome in endothelial cells senescence. Results show an increment of pro-inflammatory cytokine interleukin (IL) -1β secretion and caspase-1 activation during the senescence of endothelial cells induced by bleomycin...
January 4, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28060938/ev71-3d-protein-binds-with-nlrp3-and-enhances-the-assembly-of-inflammasome-complex
#20
Wenbiao Wang, Feng Xiao, Pin Wan, Pan Pan, Yecheng Zhang, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
Activation of NLRP3 inflammasome is important for effective host defense against invading pathogen. Together with apoptosis-associated speck-like protein containing CARD domain (ASC), NLRP3 induces the cleavage of caspase-1 to facilitate the maturation of interleukin-1beta (IL-1β), an important pro-inflammatory cytokine. IL-1β subsequently plays critical roles in inflammatory responses by activating immune cells and inducing many secondary pro-inflammatory cytokines. Although the role of NLRP3 inflammasome in immune response is well defined, the mechanism underlying its assembly modulated by pathogen infection remains largely unknown...
January 2017: PLoS Pathogens
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