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https://www.readbyqxmd.com/read/28921468/inflammasomes-in-the-gut-mucosal-homeostasis
#1
Xiaomin Yao, Guangxun Meng
Inflammasomes are critical checkpoints in inflammation. The activation of inflammasome can cause a series of inflammatory responses including maturation of interleukin (IL)-1β and IL-18 and a specialized form of cell death called pyroptosis. Since its identification in the early 2000s, inflammasomes have been implicated to play multifaceted roles in varied pathological and physiological conditions, especially in the mucosal compartments including the gut. Maintaining gut mucosal homeostasis has always been a remarkable challenge for the host due to both the vast mucosal surface that is exposed to the outside and the enormous amount of local microbiota...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921463/activation-of-the-innate-immune-receptors-guardians-of-the-micro-galaxy-activation-and-functions-of-the-innate-immune-receptors
#2
Dominic De Nardo
The families of innate immune receptors are the frontline responders to danger. These superheroes of the host immune systems populate innate immune cells, surveying the extracellular environment and the intracellular endolysosomal compartments and cytosol for exogenous and endogenous danger signals. As a collective the innate immune receptors recognise a wide array of stimuli, and in response they initiate specific signalling pathways leading to activation of transcriptional or proteolytic pathways and the production of inflammatory molecules to destroy foreign pathogens and/or resolve tissue injury...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28887037/cholecalciterol-cholesterol-emulsion-attenuates-experimental-autoimmune-myocarditis-in-mice-via-inhibition-of-the-pyroptosis-signaling-pathway
#3
Ning Liu, Han Su, Yalin Zhang, Zuwang Liu, Juan Kong
1,25-dihydroxyvitamin D3 and its analog (paricalcitol) have beneficial effects on multiple systems and diseases, including myocarditis. However, the therapeutic effect of cholecalciterol cholesterol emulsion (CCE) on myocarditis and the role of pyroptosis in the progress of myocarditis have not been determined. The objective of this study was to investigate the effect of CCE on experimental autoimmune myocarditis and its underlying mechanisms. The ratio of heart weight to body weight was decreased after CCE treatment compared with vehicle-treated controls...
September 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28882883/cytoprotective-activated-protein-c-averts-nlrp3-inflammasome-induced-ischemia-reperfusion-injury-via-mtorc1-inhibition
#4
Sumra Nazir, Ihsan Gadi, Moh'd Mohanad Al-Dabet, Ahmed Elwakiel, Shrey Kohli, Sanchita Ghosh, Jayakumar Manoharan, Satish Ranjan, Fabian Bock, Ruediger C Braun-Dullaeus, Charles T Esmon, Tobias B Huber, Eric Camerer, Chris Dockendorff, John H Griffin, Berend Isermann, Khurrum Shahzad
Cytoprotection by activated protein C (aPC) following ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation and hence conceptually cell-death forms disjunct from immunologically silent apoptosis are more likely to be relevant. As pyroptosis, cell death resulting from inflammasome activation, is typically observed in IRI we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRI...
September 7, 2017: Blood
https://www.readbyqxmd.com/read/28875942/inflammasome-dependent-mechanisms-involved-in-sensing-and-restriction-of-bacterial-replication
#5
Warrison A Andrade, Dario S Zamboni
Inflammasomes are multiprotein platforms assembled in the cytosol in response to pathogens and cell stress. Inflammasomes are recognized by their important role on defenses against bacterial infections and have been also implicated in a range of human inflammatory disorders. Intracellular sensors such as NLRP1, NLRP3, NLRC4, AIM2 and Pyrin induce assembly of inflammasomes, while caspase-11 induces the non-canonical pathway for activation of the NLRP3 inflammasome. The formation of the inflammasome leads to caspase-1 activation that triggers pyroptosis and activation of interleukin-1β (IL-1β) and IL-18...
September 6, 2017: Current Issues in Molecular Biology
https://www.readbyqxmd.com/read/28873330/differential-expression-of-virulence-genes-in-legionella-pneumophila-growing-in-acanthamoeba-and-human-monocytes
#6
Qianqian Mou, Polly H M Leung
Legionella pneumophila, the causative agent of Legionnaires' disease, is widely distributed throughout natural and artificial water systems and can replicate in macrophages and amoebae. Amoebae are the natural hosts of L. pneumophila, whereas macrophages are incidentally infected. The life cycle of L. pneumophila comprises a replicative phase within the Legionella-containing vacuole (LCV) and a transmissive phase during which bacterial cells become motile and are released via killing of the host. Although the host death mechanisms induced by L...
September 5, 2017: Virulence
https://www.readbyqxmd.com/read/28864208/a-new-mechanism-of-inhibition-of-il-1%C3%AE-secretion-by-celastrol-through-the-nlrp3-inflammasome-pathway
#7
Wenyu Xin, Qiaoyun Wang, Dan Zhang, Chaoyun Wang
The NLRP3 (NOD-like receptor protein 3) inflammasome is a caspase-1-containing multiprotein complex that controls the release of IL-1β and has been associated with the development of inflammatory diseases. Celastrol, a pharmacologically active ingredient extracted from Tripterygium wilfordii Hook, has anti-inflammatory activities based on its inhibition of IL-1β secretion. The purpose of the present study was to investigate the possible modulation of NLRP3 inflammasome-mediated IL-1β and IL-18 release from macrophages by celastrol...
August 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28861067/transcriptomic-analyses-reveal-differential-gene-expression-of-immune-and-cell-death-pathways-in-the-brains-of-mice-infected-with-west-nile-virus-and-chikungunya-virus
#8
Stephanie M Lim, Henk-Jan van den Ham, Minoushka Oduber, Eurydice Martina, Fatiha Zaaraoui-Boutahar, Jeroen M Roose, Wilfred F J van IJcken, Albert D M E Osterhaus, Arno C Andeweg, Penelope Koraka, Byron E E Martina
West Nile virus (WNV) and chikungunya virus (CHIKV) are arboviruses that are constantly (re-)emerging and expanding their territory. Both viruses often cause a mild form of disease, but severe forms of the disease can consist of neurological symptoms, most often observed in the elderly and young children, respectively, for which the mechanisms are poorly understood. To further elucidate the mechanisms responsible for end-stage WNV and CHIKV neuroinvasive disease, we used transcriptomics to compare the induction of effector pathways in the brain during the early and late stage of disease in young mice...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28855232/molecular-mechanisms-of-inflammasome-signaling
#9
REVIEW
Anukriti Mathur, Jenni A Hayward, Si Ming Man
The inflammasome is a macromolecular protein complex that mediates proteolytic cleavage of pro-IL-1β and -IL-18 and induces cell death in the form of pyroptosis. Certain nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), or tripartite motif (TRIM) family receptors trigger the assembly of an inflammasome in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Recent studies have revealed a multitude of host components and signals that are essential for controlling canonical and noncanonical inflammasome activation and pyroptosis...
August 30, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28836226/the-ketone-body-%C3%AE-hydroxybutyrate-does-not-inhibit-synuclein-mediated-inflammasome-activation-in-microglia
#10
Vandana Deora, Eduardo A Albornoz, Kevin Zhu, Trent M Woodruff, Richard Gordon
Parkinson's disease (PD) is recognized as the most common neurodegenerative movement disorder and results in debilitating motor deficits. The accumulation and spread of neurotoxic synuclein aggregates in the form of Lewy bodies is a key pathological feature of PD. Chronic activation of the NLRP3 inflammasome by protein aggregates is emerging as a major pathogenic mechanism in progressive neurodegenerative disorders and is considered an important therapeutic target. Recently the ketone body, β-hydroxy butyrate (BHB), was shown to efficiently inhibit the NLRP3 inflammasome in macrophages, and in vivo models of inflammatory disease...
August 23, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28833919/il-10-secreted-by-mesenchymal-stem-cells-attenuates-acute-liver-failure-through-inhibiting-pyroptosis
#11
Wang Jinglin, Ren Haozhen, Yuan Xianwen, Ma Hucheng, Shi Xiaolei, Ding Yitao
AIMS: Recently, the benefit of mesenchymal stem cells (MSCs) as a cell-based therapy for acute liver failure (ALF) has gained much attention, although the mechanism of action of MSCs in the treatment of ALF remains elusive. Pyroptosis is a novel form of programmed cell death with an intense inflammatory response. The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects via inhibiting pyroptosis in ALF. METHODS: MSCs obtained from C57BL/6 mice were isolated and cultured according to an established protocol...
August 22, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28826530/a-mechanistic-understanding-of-pyroptosis-the-fiery-death-triggered-by-invasive-infection
#12
Xing Liu, Judy Lieberman
Immune cells and skin and mucosal epithelial cells recognize invasive microbes and other signs of danger to sound alarms that recruit responder cells and initiate an immediate "innate" immune response. An especially powerful alarm is triggered by cytosolic sensors of invasive infection that assemble into multimolecular complexes, called inflammasomes, that activate the inflammatory caspases, leading to maturation and secretion of proinflammatory cytokines and pyroptosis, an inflammatory death of the infected cell...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28826527/chromosome-17q21-genes-ormdl3-and-gsdmb-in-asthma-and-immune-diseases
#13
Sudipta Das, Marina Miller, David H Broide
Chromosome 17q21 contains a cluster of genes including ORMDL3 and GSDMB, which have been highly linked to asthma in genome-wide association studies. ORMDL3 is localized to the endoplasmic reticulum and regulates downstream pathways including sphingolipids, metalloproteases, remodeling genes, and chemokines. ORMDL3 inhibits serine palmitoyl-CoA transferase, the rate-limiting enzyme for sphingolipid biosynthesis. In addition, ORMDL3 activates the ATF6α branch of the unfolded protein response which regulates SERCA2b and IL-6, pathways of potential importance to asthma...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28813641/aim2-inflammasome-activation-and-regulation-a-structural-perspective
#14
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/28808162/listeria-monocytogenes-and-shigella-flexneri-activate-the-nlrp1b-inflammasome
#15
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/28796264/lytic-cell-death-induced-by-melittin-bypasses-pyroptosis-but-induces-nlrp3-inflammasome-activation-and-il-1%C3%AE-release
#16
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/28783694/zbp1-dai-is-an-innate-sensor-of-influenza-virus-triggering-the-nlrp3-inflammasome-and-programmed-cell-death-pathways
#17
Teneema Kuriakose, Si Ming Man, R K Subbarao Malireddi, Rajendra Karki, Sannula Kesavardhana, David E Place, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
The interferon (IFN)-inducible protein Z-DNA binding protein 1 [ZBP1; also known as DNA-dependent activator of IFN regulatory factors (DAI) and DLM-1] was identified as a double-stranded DNA sensor, which instigates innate immune responses. However, this classification has been disputed, and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. We demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the receptor-interacting protein kinase 1 (RIPK1)-RIPK3-caspase-8 axis...
August 12, 2016: Science Immunology
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/28761045/salmonella-typhimurium-induced-il-1-release-from-primary-human-monocytes-requires-nlrp3-and-can-occur-in-the-absence-of-pyroptosis
#19
Catherine E Diamond, Keith Weng Kit Leong, Maurizio Vacca, Jack Rivers-Auty, David Brough, Alessandra Mortellaro
Large molecular complexes known as inflammasomes regulate the release of IL-1β from immune cells in response to infection and injury. Salmonella typhimurium infection is reported to activate NLRP3 and NLRC4 inflammasomes which are subsequently involved in pyroptosis of the cell and pathogen clearance. However, the response to S. typhimurium in primary human monocytes has not been studied in detail. The aim of this study was to investigate the effect of S. typhimurium on inflammasomes in primary human monocytes...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28748958/new-and-revisited-approaches-to-preserving-the-reperfused-myocardium
#20
REVIEW
Robert A Kloner, David A Brown, Marie Csete, Wangde Dai, James M Downey, Roberta A Gottlieb, Sharon L Hale, Jianru Shi
Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium...
July 27, 2017: Nature Reviews. Cardiology
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