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Inflammasome

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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/28813221/inflammatory-bowel-disease-and-the-nlrp3-inflammasome
#3
Thirumala-Devi Kanneganti
New England Journal of Medicine, Volume 377, Issue 7, Page 694-696, August 2017.
August 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28811967/il-18-receptor-marks-functional-cd8-t-cells-in-non-small-cell-lung-cancer
#4
Eleonora Timperi, Chiara Focaccetti, Daniela Gallerano, Mariangela Panetta, Sheila Spada, Enzo Gallo, Paolo Visca, Federico Venuta, Daniele Diso, Arsela Prelaj, Flavia Longo, Francesco Facciolo, Paola Nisticò, Vincenzo Barnaba
IL-18 is an inflammasome-related cytokine, member of the IL-1 family, produced by a wide range of cells in response to signals by several pathogen- or damage-associated molecular patterns. It can be highly represented in tumor patients, but its relevance in human cancer development is not clear. In this study, we provide evidence that IL-18 is principally expressed in tumor cells and, in concert with other conventional Th1 cell-driven cytokines, has a pivotal role in establishing a pro-inflammatory milieu in the tumor microenvironment of human non-small cell lung cancer (NSCLC)...
2017: Oncoimmunology
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
#5
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/28811279/zebrafish-earns-its-stripes-for-in-vivo-asc-speck-dynamics
#6
Jelena S Bezbradica, Kate Schroder
Assembly of the ASC speck is critical for signaling by the inflammasome. In this issue, Kuri et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201703103) use live microscopy to track fluorescently tagged endogenous ASC in the zebrafish, describing the molecular domains driving ASC speck assembly and identifying a key role for macrophages in ASC speck removal in vivo.
August 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28809949/maturation-dependent-expression-of-aim2-in-human-b-cells
#7
Alexandra Svensson, Marianela Patzi Churqui, Kerstin Schlüter, Liza Lind, Kristina Eriksson
Intracellular DNA- and RNA-sensing receptors, such as the IFN-inducible protein Absent in Melanoma 2 (AIM2), serve as host sensors against a wide range of infections. Immune sensing and inflammasome activation by AIM2 has been implicated in innate antiviral recognition in many experimental systems using cell-lines and animal models. However, little is known about the expression and function of AIM2 in freshly isolated human cells. In this study we investigated the expression of AIM2 in different cell types derived from human cord and adult peripheral blood, in steady state and following in vitro-activation...
2017: PloS One
https://www.readbyqxmd.com/read/28808303/nlrp3-inflammasome-activation-results-in-liver-inflammation-and-fibrosis-in-mice-infected-with-schistosoma-japonicum-in-a-syk-dependent-manner
#8
Ya-Qi Lu, Shan Zhong, Nan Meng, Yin-Ping Fan, Wang-Xian Tang
Granulomatous and fibrosing inflammation in response to soluble egg antigen (SEA) from Schistosoma japonicum (S. japonicum) is the main pathological process of S. japonicum infection. Inflammasome activation has recently been implicated in the pathogenesis of liver disease. However, the role of inflammasome activation in schistosomiasis-associated liver fibrosis (SSLF) has not been extensively studied. In this study, it is demonstrated that the NLRP3 inflammasome is markedly activated in mouse HSCs both in vivo and in vitro during S...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808241/specific-calpain-inhibition-protects-kidney-against-inflammaging
#9
Guillaume Hanouna, Laurent Mesnard, Sophie Vandermeersch, Joëlle Perez, Sandrine Placier, Jean-Philippe Haymann, Fabien Campagne, Julien Moroch, Aurélien Bataille, Laurent Baud, Emmanuel Letavernier
Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808190/cholesterol-crystal-embolization-following-plaque-rupture-a-systemic-disease-with-unusual-features
#10
Firas Ghanem, Deepthi Vodnala, Jagadeesh K Kalavakunta, Sridevi Durga, Noah Thormeier, Prem Subramaniyam, Scott Abela, George S Abela
Cholesterol crystal embolic (CCE) syndrome is often a clinically challenging condition that has a poor prognostic implication. It is a result of plaque rupture with release of cholesterol crystals into the circulation that embolize into various tissue organs. Plaque rupture seems to be triggered by an expanding necrotic core during cholesterol crystallization forming sharp tipped crystals that perforate and tear the fibrous cap. Embolizing cholesterol crystals then initiate both local and systemic inflammation that eventually lead to vascular fibrosis and obstruction causing symptoms that can mimic other vasculitic conditions...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808162/listeria-monocytogenes-and-shigella-flexneri-activate-the-nlrp1b-inflammasome
#11
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/28805975/antofine-suppresses-endotoxin-induced-inflammation-and-metabolic-disorder-via-amp-activated-protein-kinase
#12
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/28801232/nlrp6-and-asc-dependent-inflammasomes-do-not-shape-the-commensal-gut-microbiota-composition
#13
Michail Mamantopoulos, Francesca Ronchi, Filip Van Hauwermeiren, Sara Vieira-Silva, Bahtiyar Yilmaz, Liesbet Martens, Yvan Saeys, Stefan K Drexler, Amir S Yazdi, Jeroen Raes, Mohamed Lamkanfi, Kathy D McCoy, Andy Wullaert
The gut microbiota regulate susceptibility to multiple human diseases. The Nlrp6-ASC inflammasome is widely regarded as a hallmark host innate immune axis that shapes the gut microbiota composition. This notion stems from studies reporting dysbiosis in mice lacking these inflammasome components when compared with non-littermate wild-type animals. Here, we describe microbial analyses in inflammasome-deficient mice while minimizing non-genetic confounders using littermate-controlled Nlrp6-deficient mice and ex-germ-free littermate-controlled ASC-deficient mice that were all allowed to shape their gut microbiota naturally after birth...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28799902/innate-immunity-to-intracellular-pathogens-balancing-microbial-elimination-and-inflammation
#14
REVIEW
Gabriel Mitchell, Ralph R Isberg
Recent excitement regarding immune clearance of intracellular microorganisms has focused on two systems that maintain cellular homeostasis. One system includes cellular autophagy components that mediate degradation of pathogens in membrane-bound compartments, in a process termed xenophagy. The second system is driven by interferon-regulated GTPases that promote rupture of pathogen-containing vacuoles and microbial degradation. In the case of xenophagy, pathogen sequestration and compartmentalization suppress inflammation...
August 9, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28799242/negative-regulation-of-nlrp3-inflammasome-activation-by-tim-3-protects-against-peritonitis
#15
Wei Wang, Qingzhu Shi, Shuaijie Dou, Ge Li, Xinhui Shi, Xingwei Jiang, Zhiding Wang, Dandan Yu, Guojiang Chen, Wang Ren Xi, He Xiao, Chunmei Hou, Jiannan Feng, Beifen Shen, Yuanfang Ma, Gencheng Han
The NLRP3 inflammasome plays roles in host defense against invading pathogens and in the development of autoimmune damage. Strict regulation of these responses is important to avoid detrimental effects. Here, we demonstrate that Tim-3, an immune checkpoint inhibitor, inhibits NLRP3 inflammasome activation by damping basal and LPS-induced NF-κB-mediated upregulation of NLRP3 and IL-1β during the priming step and basal and ATP/LPS-induced ATP production, K(+) efflux, and ROS production during the activation step...
August 11, 2017: Immunology
https://www.readbyqxmd.com/read/28798666/nlrp6-inflammasome-ameliorates-brain-injury-after-intracerebral-hemorrhage
#16
Peng-Fei Wang, Zhen-Guang Li, Yong Zhang, Xiao-Hua Ju, Xin-Wu Liu, Ai-Ming Zhou, Jing Chen
NLRP6 inflammasome, one of the important intracellular innate immune sensors, has been shown to regulate immune responses. However, its roles in the intracerebral hemorrhage (ICH) are completely not clear. In the present study, we investigated the expression profile and biological roles of NLRP6 inflammasome in perihematomal brain tissues of mice subjected to ICH. In this study, we investigated the expression profile of NLRP6 inflammasome in the perihematomal brain tissues and explored the biological role of NLRP6 inflammasome upon acute brain injury in mice subjected to ICH...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28798231/p2x7-receptor-antagonism-prevents-il-1%C3%AE-release-from-salivary-epithelial-cells-and-reduces-inflammation-in-a-mouse-model-of-autoimmune-exocrinopathy
#17
Mahmoud G Khalafalla, Lucas T Woods, Jean M Camden, Aslam A Khan, Kirsten H Limesand, Michael J Petris, Laurie Erb, Gary A Weisman
Salivary gland inflammation is a hallmark of Sjogrens syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated non-selective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1β and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28796840/yes-research-matters
#18
Mari L Shinohara
My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In his case, the diagnosis started from a suggestion by his doctor to check whether he had a gastric infection with Helicobacter pylori, a bacterial species found in the digestive tract. In Japan, where he lives, a majority of gastric cancer patients (more than 99%) have been infected with H...
August 2017: PLoS Pathogens
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
#19
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/28794421/beta-hydroxybutyrate-an-endogenic-nlrp3-inflammasome-inhibitor-attenuates-stress-induced-behavioral-and-inflammatory-responses
#20
Takehiko Yamanashi, Masaaki Iwata, Naho Kamiya, Kyohei Tsunetomi, Naofumi Kajitani, Nodoka Wada, Takahiro Iitsuka, Takahira Yamauchi, Akihiko Miura, Shenghong Pu, Yukihiko Shirayama, Ken Watanabe, Ronald S Duman, Koichi Kaneko
Neuro-inflammation has been shown to play a critical role in the development of depression. Beta-hydroxybutyrate (BHB) is a ketone body and has recently been reported to exert anti-inflammatory effects via inhibition of NLRP3 inflammasome. Here, we investigated the potential antidepressant and anti-inflammatory effects of BHB on rats exposed to acute and chronic stress. We examined the influence of repeated BHB administration on depressive and anxiety behaviors in a rodent model of chronic unpredictable stress (CUS)...
August 9, 2017: Scientific Reports
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