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Inflammasome

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https://www.readbyqxmd.com/read/28447181/sglt-2-inhibition-with-dapagliflozin-reduces-the-activation-of-the-nlrp3-asc-inflammasome-and-attenuates-the-development-of-diabetic-cardiomyopathy-in-mice-with-type-2-diabetes-further-augmentation-of-the-effects-with-saxagliptin-a-dpp4-inhibitor
#1
Yumei Ye, Mandeep Bajaj, Hsiu-Chiung Yang, Jose R Perez-Polo, Yochai Birnbaum
PURPOSE: We assessed whether (1) dapagliflozin (Dapa, an SGLT2-inhibitor) attenuates the deterioration of heart function Nlrp3 and inflammasome activation in diabetic mice. (2) The effects can be augmented with saxagliptin (Saxa), a DDP4-inhibitor. (3) Dapa effect is possibly SGLT2-independent on cardiofibroblasts in vitro. METHODS: Type 2 diabetic (BTBR ob/ob) and wild-type (WT) mice received vehicle, Dapa, or Dapa+Saxa for 8 weeks. Glucose tolerance test and echocardiogram were performed...
April 26, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#2
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28438165/microglia-derived-il-1%C3%AE-promotes-chemokine-expression-by-m%C3%A3-ller-cells-and-rpe-in-focal-retinal-degeneration
#3
Riccardo Natoli, Nilisha Fernando, Michele Madigan, Joshua A Chu-Tan, Krisztina Valter, Jan Provis, Matt Rutar
BACKGROUND: Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we explore the role of interleukin-1β (IL-1β) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10 during photo-oxidative retinal damage, and the effect on both the accumulation of outer-retinal macrophages, and death of photoreceptors. METHODS: Inhibition of retinal IL-1β expression was performed using either siRNA or antibody neutralisation, which was intravitreally injected in SD rats prior to photo-oxidative damage...
April 24, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28437591/fluorofenidone-attenuates-il-1%C3%AE-production-by-interacting-with-nlrp3-inflammasome-in-unilateral-ureteral-obstruction
#4
Linfeng Zheng, Jin Zhang, Xiangning Yuan, Juan Tang, Sisi Qiu, Zhangzhe Peng, Qiongjing Yuan, Yanyun Xie, Wenjuan Mei, Yiting Tang, Jie Meng, Gaoyun Hu, Lijian Tao
AIM: We explored whether Fluorofenidone reduced IL-1β production by interacting with NLRP3 inflammasome in unilateral ureteral obstruction (UUO). METHODS: UUO rats were treated with Fluorofenidone (500 mg · kg · d) for 3, 7 days. Morphologic analysis and leukocytes infiltration were assessed in ligated kidneys. Furthermore, plasmids of NLRP3, ASC, pro-Caspase-1, pro-IL-1β were co-transfected into 293 T cells, and then treated with Fluorofenidone (2 mM)...
April 24, 2017: Nephrology
https://www.readbyqxmd.com/read/28437586/pathogenesis-of-vascular-leak-in-dengue-virus-infection
#5
REVIEW
Gathsaurie Neelika Malavige, Graham S Ogg
Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident during 3-6 days since the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24 to 48 hours and usually shows rapid and complete reversal, suggesting it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as TNFα, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors...
April 24, 2017: Immunology
https://www.readbyqxmd.com/read/28435131/repression-of-acetaminophen-induced-hepatotoxicity-by-a-combination-of-celastrol-and-brilliant-blue-g
#6
Heba A Abdelaziz, Mohamed E Shaker, Mohamed F Hamed, Nariman M Gameil
The sterile inflammatory response is an eminent contributor to acetaminophen (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of signaling events preceded the NLRP3-inflammasome activation, like the transcription factor NF-κB and the purinergic receptor P2×7, is still unclear and needs further elucidation. Here, we investigated the pharmacological inhibition of these upstream signaling molecules by celastrol and brilliant blue G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice...
April 20, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28432355/basal-autophagy-prevents-autoactivation-or-enhancement-of-inflammatory-signals-by-targeting-monomeric-myd88
#7
Takeshi Into, Toshi Horie, Megumi Inomata, Jin Gohda, Jun-Ichiro Inoue, Yukitaka Murakami, Shumpei Niida
Autophagy, the processes of delivery of intracellular components to lysosomes, regulates induction of inflammation. Inducible macroautophagy degrades inflammasomes and dysfunctional mitochondria to downregulate inflammatory signals. Nonetheless, the effects of constitutive basal autophagy on inflammatory signals are largely unknown. Here, we report a previously unknown effect of basal autophagy. Lysosomal inhibition induced weak inflammatory signals in the absence of a cellular stimulus and in the presence of a nutrient supply, and their induction was impaired by MyD88 deficiency...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432035/expression-of-pattern-recognition-receptors-and-activation-of-the-non-canonical-inflammasome-pathway-in-brain-pericytes
#8
Ádám Nyúl-Tóth, Mihály Kozma, Péter Nagyőszi, Krisztina Nagy, Csilla Fazakas, János Haskó, Kinga Molnár, Attila E Farkas, Attila G Végh, György Váró, Péter Galajda, Imola Wilhelm, István A Krizbai
Cerebral pericytes are mural cells embedded in the basement membrane of capillaries. Increasing evidence suggests that they play important role in controlling neurovascular functions, i.e. cerebral blood flow, angiogenesis and permeability of the blood-brain barrier. These cells can also influence neuroinflammation which is highly regulated by the innate immune system. Therefore, we systematically tested the pattern recognition receptor expression of brain pericytes. We detected expression of NOD1, NOD2, NLRC5, NLRP1-3, NLRP5, NLRP9, NLRP10 and NLRX mRNA in non-treated cells...
April 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28430665/p2x7-receptor-and-nlrp3-inflammasome-activation-in-head-and-neck-cancer
#9
Ju Young Bae, Sang-Woo Lee, Yong-Hwan Shin, Jong-Ho Lee, Jeong Won Jahng, Kyungpyo Park
In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in head and neck cancer. We found upregulation of purinergic receptor P2X7 and all NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis-associated speck-like protein containing CARD, and pro-form caspase 1 in A253 cells derived from epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429343/post-prandial-effects-of-hazelnut-enriched-high-fat-meal-on-ldl-oxidative-status-oxidative-and-inflammatory-gene-expression-of-healthy-subjects-a-randomized-trial
#10
L Di Renzo, G Merra, R Botta, P Gualtieri, A Manzo, M A Perrone, M Mazza, S Cascapera, A De Lorenzo
OBJECTIVE: Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. Micronutrients modulate the immune system and exert a protective action by reducing low-density lipoproteins oxidation (ox-LDL) via induction of antioxidant enzymes. SUBJECTS AND METHODS: The clinical study was a randomized and cross-over trial, conducted through the CONSORT flowchart...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428988/polydatin-attenuates-potassium-oxonate-induced-hyperuricemia-and-kidney-inflammation-by-inhibiting-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-via-the-ampk-sirt1-pathway
#11
Lvyi Chen, Zhou Lan
This study was designed to investigate the effects of polydatin (PLD) on potassium oxonate-induced hyperuricemic rats. Hyperuricemic rats were treated with potassium oxonate (250 mg kg(-1)) intragastrically for 7 days, and polydatin (25, 50 mg kg(-1)) or allopurinol (5 mg kg(-1)) was administered to the rats 1 h after the potassium oxonate exposure. Polydatin administration decreased the levels of uric acid and creatinine in serum and urine, leading to inhibition of pro-inflammatory cytokine production in serum and kidney...
April 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28428961/glucose-insulin-potassium-alleviates-intestinal-mucosal-barrier-injuries-involving-decreased-expression-of-uncoupling-protein-2-and-nlr-family-pyrin-domain-containing-3-inflammasome-in-polymicrobial-sepsis
#12
Jun-Liang Zhang, Yi-Ting Chen, Guang-Dao Chen, Tao Wang, Ju-Xin Zhang, Qi-Yi Zeng
Uncoupling protein 2 (UCP2) may be critical for intestinal barrier function which may play a key role in the development of sepsis, and insulin has been reported to have anti-inflammatory effects. Male Sprague-Dawley rats were randomly allocated into five groups: control group, cecal ligation and puncture (CLP) group, sham surgery group, CLP plus glucose-insulin-potassium (GIK) group, and CLP plus glucose and potassium (GK) group. Ileum tissues were collected at 24 h after surgery. Histological and cytokine analyses, intestinal permeability tests, and western blots of intestinal epithelial tight junction component proteins and UCP2 were performed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28427559/stress-induced-nlrp3-inflammasome-in-human-diseases
#13
Elísabet Alcocer-Gómez, Beatriz Castejón-Vega, Mario D Cordero
Stress is a complex event that induces disturbances to physiological and psychological homeostasis, and it may have a detrimental impact on certain brain and physiological functions. In the last years, a dual role of the stress effect has been studied in order to elucidate the molecular mechanism by which can induce physiological symptoms after psychological stress exposition and vice versa. In this sense, inflammation has been proposed as an important starring. And in the same line, the inflammasome complex has emerged to give responses because of its role of stress sensor...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427239/foxo3a-dependent-bim-transcription-protects-mice-from-a-high-fat-diet-via-inhibition-of-activation-of-the-nlrp3-inflammasome-by-facilitating-autophagy-flux-in-kupffer-cells
#14
Liu Yan, Zhang Wenfeng, Wu Xiaoling, Gong Jianping
BACKGROUND: The role of Foxo3a in the regulation of autophagy flux and activation of the NLRP3 inflammasome in KCs suffering from HFD conditions is unknown. RESULTS: Up-regulation of Foxo3a restored autophagy flux and dampened the activation of the NLRP3 inflammasome in KCs stimulated with PA and LPS. In contrast, down-regulation of Foxo3a increased blockage of autophagy flux and promoted NLRP3 inflammasome activation. Additionally, mRNA levels of Bim were significantly changed with the alteration of Foxo3a in KCs under PA and LPS stimulation among foxo3a targeted genes...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#15
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/28424239/aim2-inflammasome-is-critical-for-influenza-induced-lung-injury-and-mortality
#16
Hongbo Zhang, Jiadi Luo, John F Alcorn, Kong Chen, Songqing Fan, Joseph Pilewski, Aizhong Liu, Wei Chen, Jay K Kolls, Jieru Wang
The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28423339/germ-cell-specific-inflammasome-component-nlrp14-negatively-regulates-cytosolic-nucleic-acid-sensing-to-promote-fertilization
#17
Takayuki Abe, Albert Lee, Ramaswami Sitharam, Jordan Kesner, Raul Rabadan, Sagi D Shapira
Cytosolic sensing of nucleic acids initiates tightly regulated programs to limit infection. Oocyte fertilization represents a scenario wherein inappropriate responses to exogenous yet non-pathogen-derived nucleic acids would have negative consequences. We hypothesized that germ cells express negative regulators of nucleic acid sensing (NAS) in steady state and applied an integrated data-mining and functional genomics approach to identify a rheostat of DNA and RNA sensing-the inflammasome component NLRP14. We demonstrated that NLRP14 interacted physically with the nucleic acid sensing pathway and targeted TBK1 (TANK binding kinase 1) for ubiquitination and degradation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28422993/th17-micro-milieu-regulates-nlrp1-dependent-caspase-5-activity-in-skin-autoinflammation
#18
Stephanie Zwicker, Eva Hattinger, Daniela Bureik, Aleksandra Batycka-Baran, Andreas Schmidt, Peter-Arne Gerber, Simon Rothenfusser, Michel Gilliet, Thomas Ruzicka, Ronald Wolf
IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7)...
2017: PloS One
https://www.readbyqxmd.com/read/28421077/human-scavenger-receptor-a1-mediated-inflammatory-response-to-silica-particle-exposure-is-size-specific
#19
Nobuo Nishijima, Toshiro Hirai, Kazuki Misato, Michihiko Aoyama, Etsushi Kuroda, Ken J Ishii, Kazuma Higashisaka, Yasuo Yoshioka, Yasuo Tsutsumi
The application of nanotechnology in the health care setting has many potential benefits; however, our understanding of the interactions between nanoparticles and our immune system remains incomplete. Although many of the biological effects of nanoparticles are negatively correlated with particle size, some are clearly size specific and the mechanisms underlying these size-specific biological effects remain unknown. Here, we examined the pro-inflammatory effects of silica particles in THP-1 cells with respect to particle size; a large overall size range with narrow intervals between particle diameters (particle diameter: 10, 30, 50, 70, 100, 300, and 1,000 nm) was used...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420825/colchicine-improves-survival-left-ventricular-remodeling-and-chronic-cardiac-function-after-acute-myocardial-infarction
#20
Koichiro Fujisue, Koichi Sugamura, Hirofumi Kurokawa, Junichi Matsubara, Masanobu Ishii, Yasuhiro Izumiya, Koichi Kaikita, Seigo Sugiyama
BACKGROUND: Several studies have reported that colchicine attenuated the infarct size and inflammation in acute myocardial infarction (MI). However, the sustained benefit of colchicine administration on survival and cardiac function after MI is unknown. It was hypothesized that the short-term treatment with colchicine could improve survival and cardiac function during the recovery phase of MI.Methods and Results:MI was induced in mice by permanent ligation of the left anterior descending coronary artery...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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