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https://www.readbyqxmd.com/read/28814068/the-activation-of-nlrp3-inflammsome-by-stimulation-of-diesel-exhaust-particles-in-lung-tissues-from-emphysema-model-and-raw-264-7-cell-line
#1
Soo-Taek Uh, So My Koo, Yangki Kim, Kiup Kim, Sungwoo Park, An Soo Jang, Dojin Kim, Yong Hoon Kim, Choon-Sik Park
Background/Aims: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. Methods: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1β (IL-1β), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry...
August 18, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28813641/aim2-inflammasome-activation-and-regulation-a-structural-perspective
#2
Bing Wang, Qian Yin
Absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple steps is the assembly of high-order structures, especially helical filaments nucleated by upstream molecules, rather than stoichiometric complexes...
August 13, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28811681/osteopontin-impacts-west-nile-virus-pathogenesis-and-resistance-by-regulating-inflammasome-components-and-cell-death-in-the-central-nervous-system-at-early-time-points
#3
Nikki Bortell, Claudia Flynn, Bruno Conti, Howard S Fox, Maria Cecilia G Marcondes
Osteopontin (OPN) is a molecule that is common in central nervous system (CNS) pathologies, which participates in the activation, migration, and survival of inflammatory cells. However, the mechanisms by which OPN modulates inflammatory pathways are not clear. To understand the role of OPN in CNS viral infections, we used a lethal mouse model of West Nile virus (WNV), characterized by the injection of high doses of the Eg101 strain of WNV, causing the increase of OPN levels in the brain since early time points...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28808162/listeria-monocytogenes-and-shigella-flexneri-activate-the-nlrp1b-inflammasome
#4
Jana Neiman-Zenevich, Sarah Stuart, Mena Abdel-Nour, Stephen E Girardin, Jeremy Mogridge
Activation of the innate immune receptor NLRP1B leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. One of the signals to which NLRP1B responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. NLRP1B might, therefore, sense microbial infection as intracellular pathogens such as Listeria monocytogenes and Shigella flexneri cause metabolic stress as a result of nutrient scavenging and host cell damage...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28807721/selenopheno-quinolinones-and-coumarins-promote-cancer-cell-apoptosis-by-ros-depletion-and-caspase-7-activation
#5
Ilona Domracheva, Iveta Kanepe-Lapsa, Ludmila Jackevica, Jelena Vasiljeva, Pavel Arsenyan
AIM: This study was designed to investigate the mechanism underlying cancer cell apoptosis caused by selenophenoquinolinones and coumarins. MATERIALS AND METHODS: Twelve derivatives were studied according to their ability to suppress the proliferation of cancer cells in vitro (i.e., HepG2, MH-22A, MCF-7), induce cell apoptosis, modulate cellular antioxidant enzyme system activities (i.e., SOD, GPx, TrxR), influence the level of ROS, and modulate caspase activity...
August 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/28805975/antofine-suppresses-endotoxin-induced-inflammation-and-metabolic-disorder-via-amp-activated-protein-kinase
#6
Shao-Ting Chou, Fang Jung, Shih-Hsing Yang, Hwei-Ling Chou, Guey-Mei Jow, Jau-Chen Lin
The inhibition of activated macrophages has been used to develop anti-inflammatory agents for therapeutic intervention to human diseases that cause excessive inflammatory responses. Antofine, a phenanthroindolizidine alkaloid, has a potent anti-inflammatory effect. However, the molecular mechanisms of its anti-inflammatory activity have not yet been fully detailed. In this study, we comprehensively explored the anti-inflammatory effects of antofine on endotoxin-induced inflammation in macrophages using cDNA microarray analysis, thereby elucidating the potential mechanism by which antofine suppresses inflammation...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805067/the-lncrna-nespas-is-associated-with-osteoarthritis-progression-and-serves-as-a-potential-new-prognostic-biomarker
#7
Sujung Park, Myeungsoo Lee, Churl-Hong Chun, Eun-Jung Jin
INTRODUCTION: In this article, we explored the hypothesis that the long noncoding RNA, Nespas, promotes osteoarthritis (OA) by supporting abnormal lipid metabolism in human chondrocytes. MATERIALS AND METHODS: Human articular chondrocytes from osteoarthritis patients were used and expression level of Nespas were determined by real-time polymerase chain reaction. Introduction of Nespas and Nespas-associated genes/miRNAs were performed by using a lentiviral system...
August 1, 2017: Cartilage
https://www.readbyqxmd.com/read/28801921/autophagy-impairment-by-caspase-1-dependent-inflammation-mediates-memory-loss-in-response-to-%C3%AE-amyloid-peptide-accumulation
#8
Lourdes Álvarez-Arellano, Martha Pedraza-Escalona, Tonali Blanco-Ayala, Nohemí Camacho-Concha, Javier Cortés-Mendoza, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
β-Amyloid peptide accumulation in the cortex and in the hippocampus results in neurodegeneration and memory loss. Recently, it became evident that the inflammatory response triggered by β-Amyloid peptides promotes neuronal cell death and degeneration. In addition to inflammation, β-Amyloid peptides also induce alterations in neuronal autophagy, eventually leading to neuronal cell death. Thus, here we evaluated whether the inflammatory response induced by the β-Amyloid peptides impairs memory via disrupting the autophagic flux...
August 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28800542/digitoflavone-dg-attenuates-lps-induced-acute-lung-injury-through-reducing-oxidative-stress-and-inflammatory-response-dependent-on-the-suppression-of-txnip-nlrp3-and-nf-%C3%AE%C2%BAb
#9
Min Meng
Acute lung injury is a severe disease with a high rate of mortality. Digitoflavone (DG) was suggested to possess bioactivities to reduce oxidative stress, inflammation and to regulate apoptosis. In our study, the normal saline, a low dose of DG (12.5mg/kg), a medium dose of DG (25mg/kg) and a high dose of DG (50mg/kg) were administered to male C57BL/6 mice by gavage. And then, the mice were intratracheally injected with either normal saline or lipopolysaccharide (LPS). We found that DG ameliorated LPS-induced lung injury and platelets activation, accompanied with reduced CD41 expression and neutrophil platelet aggregates (NPAs)...
August 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28798291/function-of-nlrp3-in-the-pathogenesis-and-development-of-diabetic-nephropathy
#10
Ying Fu, Nannan Wu, Dong Zhao
BACKGROUND The aim of this research was to study the function of NLRP3 in the pathogenesis and development of diabetic nephropathy (DN). MATERIAL AND METHODS We compared the expression of NLRP3-related protein in human glomerular mesangial cells under high glucose conditions at different times and in rats with DN of different ages. We also compared changes in IL-18 and IL-1β expression levels at different stages of DN. RESULTS After six hours, 12 hours, and 24 hours of high glucose stimulation, the secretion of IL-1β in human glomerular mesangial cells, compared to unstimulated cells, was 1...
August 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28796264/lytic-cell-death-induced-by-melittin-bypasses-pyroptosis-but-induces-nlrp3-inflammasome-activation-and-il-1%C3%AE-release
#11
Fátima Martín-Sánchez, Juan José Martínez-García, María Muñoz-García, Miriam Martínez-Villanueva, José A Noguera-Velasco, David Andreu, Luís Rivas, Pablo Pelegrín
The nucleotide-binding domain and leucine-rich repeat-containing receptor with a pyrin domain 3 (NLRP3) inflammasome is a sensor for different types of infections and alterations of homeostatic parameters, including abnormally high levels of the extracellular nucleotide ATP or crystallization of different metabolites. All NLRP3 activators trigger a similar intracellular pathway, where a decrease in intracellular K(+) concentration and permeabilization of plasma membrane are key steps. Cationic amphipathic antimicrobial peptides and peptide toxins permeabilize the plasma membrane...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#12
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790324/the-h7n9-influenza-a-virus-infection-results-in-lethal-inflammation-in-the-mammalian-host-via-the-nlrp3-caspase-1-inflammasome
#13
Rongrong Ren, Shuxian Wu, Jialin Cai, Yuqin Yang, Xiaonan Ren, Yanling Feng, Lixiang Chen, Boyin Qin, Chunhua Xu, Hua Yang, Zhigang Song, Di Tian, Yunwen Hu, Xiaohui Zhou, Guangxun Meng
The avian origin influenza A virus (IAV) H7N9 has caused a considerable number of human infections associated with high rates of death since its emergence in 2013. As a vital component of the host innate immune system, the nucleotide-binding domain leucine-rich repeat containing receptor, pyrin domain containing 3 (NLRP3) inflammasome plays a critical role against H1N1 viral infection. However, the function of NLRP3 inflammasome in host immunological responses to the lethal H7N9 virus is still obscure. Here, we demonstrated that mice deficient for NLRP3 inflammasome components, including NLRP3, caspase-1, and Apoptosis-associated speck-like protein containing a CARD (ASC), were less susceptible to H7N9 viral challenge than wild type (WT) controls...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783696/il-1%C3%AE-is-an-innate-immune-sensor-of-microbial-proteolysis
#14
Christopher N LaRock, Jordan Todd, Doris L LaRock, Joshua Olson, Anthony J O'Donoghue, Avril A B Robertson, Matthew A Cooper, Hal M Hoffman, Victor Nizet
Interleukin-1β (IL-1β) is a key proinflammatory cytokine that drives antimicrobial immune responses. IL-1β is aberrantly activated in autoimmune diseases, and IL-1β inhibitors are used as therapeutic agents to treat patients with certain autoimmune disorders. Review of postmarketing surveillance of patients receiving IL-1β inhibitors found a disproportionate reporting of invasive infections by group A Streptococcus (GAS). IL-1β inhibition increased mouse susceptibility to GAS infection, but IL-1β was produced independent of canonical inflammasomes...
August 19, 2016: Science Immunology
https://www.readbyqxmd.com/read/28783585/downregulated-nlrp3-and-nlrp1-inflammasomes-signaling-pathways-in-the-development-and-progression-of-type-1-diabetes-mellitus
#15
Huawei Liu, Ruiying Xu, Qingyu Kong, Jiling Liu, Zhen Yu, Cuifen Zhao
BACKGROUND: NLRP3 and NLRP1 inflammasomes signaling pathways may play an important role in the development and progression of type 1 diabetes mellitus (T1DM). However, relative research is rare. METHODS: The blood mononuclear cells (PBMCs) and granulocytes (GCs) were collected from T1DM patients. The mRNA and protein expression levels were detected by qRT-PCR and Western blotting, respectively. The NLRP3/NLRP1was knocked down by transfected with siRNA, or ovexpressed by infected with lentiviral vectors in PBMCs and GCs from non obese diabetic (NOD) mice, respectively...
August 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28782714/electroacupuncture-inhibits-nlrp3-inflammasome-activation-through-cb2-receptors-in-inflammatory-pain
#16
Fang Gao, Hong-Chun Xiang, Hong-Ping Li, Min Jia, Xiao-Li Pan, Hui-Lin Pan, Man Li
The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically. The inflammasome promotes the maturation of the inflammatory cytokines, and EA can stimulate cannabinoid CB2 receptors in inflamed tissues. In this study we investigated whether EA inhibits NLRP3 inflammasome activation through CB2 receptors and thus relieving inflammatory pain. Assay of Caspase-1 activity and western blotting revealed that complete Freund's adjuvant (CFA) injection activated the NLRP3 inflammasome in the skin tissue in rats, which was attenuated by EA treatment...
August 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28782532/ghrelin-protects-the-heart-against-ischemia-reperfusion-injury-via-inhibition-of-tlr4-nlrp3-inflammasome-pathway
#17
Qin Wang, Ping Lin, Peng Li, Li Fen, Qian Ren, Xiaofeng Xie, Jing Xu
AIMS: The aim of this study was to investigate the cardioprotective effects of ghrelin against myocardial ischemia/reperfusion (I/R) injury and the underlying mechanism. MAIN METHODS: Sprague-Dawley rats were randomized into Sham, I/R and I/R+ghrelin groups. After 30 minutes ischemia, ghrelin (8nmol/kg) was injected intraperitoneally at the time of reperfusion in the I/R+ghrelin group. Then hemodynamic parameters were observed at 24h after reperfusion. KEY FINDINGS: Ghrelin exhibited dramatic improvement in cardiac functions, as manifested by increased LVSP and ±dP/dtmax and decreased LVDP...
August 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28771586/inhibition-of-caspase-1-or-gasdermin-d-enable-caspase-8-activation-in-the-naip5-nlrc4-asc-inflammasome
#18
Danielle P A Mascarenhas, Daiane M Cerqueira, Marcelo S F Pereira, Fernanda V S Castanheira, Talita D Fernandes, Graziele Z Manin, Larissa D Cunha, Dario S Zamboni
Legionella pneumophila is a Gram-negative, flagellated bacterium that survives in phagocytes and causes Legionnaires' disease. Upon infection of mammalian macrophages, cytosolic flagellin triggers the activation of Naip/NLRC4 inflammasome, which culminates in pyroptosis and restriction of bacterial replication. Although NLRC4 and caspase-1 participate in the same inflammasome, Nlrc4-/- mice and their macrophages are more permissive to L. pneumophila replication compared with Casp1/11-/-. This feature supports the existence of a pathway that is NLRC4-dependent and caspase-1/11-independent...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28768565/caspase-2-mediates-triglyceride-tg-induced-macrophage-cell-death
#19
Jaewon Lim, Sung Hoon Kim, Hyun-Kyung Kim, Ki-Jong Rhee, Yoon Suk Kim
Triglyceride (TG) accumulation causes macrophage cell death, which affects the development of atherosclerosis. Here, we examined whether caspase-2 is implicated in TG-induced macrophage cell death. We found that caspase-2 activity is increased in TG-treated THP-1 macrophages, and that inhibition of caspase-2 activity drastically inhibits TG-induced cell death. We previously reported that TG-induced macrophage death is triggered by caspase-1, and thus investigated the relationship between casapse-2 and caspase-1 in TG-induced macrophage cell death...
August 3, 2017: BMB Reports
https://www.readbyqxmd.com/read/28766178/differential-regulation-of-il-1%C3%AE-and-il-6-release-in-murine-macrophages
#20
Seishiro Hirano, Quan Zhou, Akiko Furuyama, Sanae Kanno
Asbestos and silica (exogenous danger) and adenosine triphosphate (ATP, endogenous danger-signaling molecule) synergistically increase IL-1β release from endotoxin-primed macrophage, which is mediated by NOD-like receptor protein 3 (NLRP3) inflammasome. However, the conversion of pro-IL-1β to its active form seems to depend on the macrophage cell types. In the present study, bone marrow-derived macrophages (BMM) and three murine macrophage cell lines, J774.1, J774A.1, and RAW264.7 were exposed to ATP or fibrous titanium dioxide (FTiO2) in the presence or absence of lipopolysaccharide (LPS), and the concentrations of IL-1β and IL-6 in both cell lysates and in the culture media were measured by immunoblotting to differentiate active form of IL-1β from pro-IL-1β...
August 1, 2017: Inflammation
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