Orchestration of Human Macrophage NLRP3 Inflammasome Activation by Staphylococcus Aureus Extracellular Vesicles
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Inflammasome Activation-Induced Hypercoagulopathy
cells Review Inflammasome Activation-Induced Hypercoagulopathy: Impact on Cardiovascular Dysfunction Triggered in COVID-19 Patients Lealem Gedefaw, Sami Ullah, Polly H. M. Leung , Yin Cai, Shea-Ping Yip * and Chien-Ling Huang * Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China; [email protected] (L.G.); [email protected] (S.U.); [email protected] (P.H.M.L.); [email protected] (Y.C.) * Correspondence: [email protected] (S.-P.Y.); [email protected] (C.-L.H.) Abstract: Coronavirus disease 2019 (COVID-19) is the most devastating infectious disease in the 21st century with more than 2 million lives lost in less than a year. The activation of inflammasome in the host infected by SARS-CoV-2 is highly related to cytokine storm and hypercoagulopathy, which significantly contribute to the poor prognosis of COVID-19 patients. Even though many studies have shown the host defense mechanism induced by inflammasome against various viral infections, mechanistic interactions leading to downstream cellular responses and pathogenesis in COVID-19 remain unclear. The SARS-CoV-2 infection has been associated with numerous cardiovascular disor- ders including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. The inflammatory response triggered by the activation of NLRP3 inflammasome under certain car- diovascular conditions resulted in hyperinflammation or the modulation of angiotensin-converting enzyme 2 signaling pathways. Perturbations of several target cells and tissues have been described in inflammasome activation, including pneumocytes, macrophages, endothelial cells, and dendritic cells. Citation: Gedefaw, L.; Ullah, S.; Leung, P.H.M.; Cai, Y.; Yip, S.-P.; The interplay between inflammasome activation and hypercoagulopathy in COVID-19 patients is an Huang, C.-L. -
Inflammasome Function in Neutrophils Kaiwen Chen Bachelor of Science (Honours Class I)
Inflammasome function in neutrophils Kaiwen Chen Bachelor of Science (Honours Class I) A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2015 Institute for Molecular Bioscience i ii Abstract The innate immune system protects against infection but also drives inflammatory disorders. Key molecular drivers of both processes are ‘inflammasomes’, multi-protein complexes that assemble in the cytosol to activate the protease, caspase-1. Active caspase-1 cleaves specific proinflammatory cytokines [e.g. interleukin (IL)-1β] into their mature, secreted forms, and initiates a form of inflammatory cell lysis called pyroptosis. Inflammasomes are assembled by select pattern recognition receptors such as NLRC4, NLRP3, AIM2, or via a non-canonical pathway involving caspase-11. Whilst inflammasomes functions have been intensely researched, the cell types mediating inflammasome signalling in distinct in vivo settings were unclear. Neutrophils are one of the first cells to arrive to a site of infection or injury, and thus have the opportunity to detect inflammasome-activating molecules in vivo, but their ability to signal by inflammasome pathways had not been closely examined. This thesis offers a detailed investigation of NLRC4, NLRP3 and caspase-11 inflammasome signalling in neutrophils during in vitro or in vivo challenge with whole microbe, purified microbial components, or adjuvant. This thesis demonstrates that acute Salmonella infection triggered NLRC4-dependent caspase-1 activation and IL-1β processing in neutrophils, and neutrophils were a major cellular compartment for IL-1β production during acute Salmonella challenge in vivo. Importantly, neutrophils did not undergo pyroptotic cell death upon NLRC4 activation, allowing these cells to sustain IL-1β production at a site of infection without compromising their crucial inflammasome-independent antimicrobial effector functions. -
NLRP3-Inflammasome Inhibition During Respiratory Virus Infection
viruses Article NLRP3-Inflammasome Inhibition during Respiratory Virus Infection Abrogates Lung Immunopathology and Long-Term Airway Disease Development Carrie-Anne Malinczak 1 , Charles F. Schuler 2,3, Angela J. Duran 1, Andrew J. Rasky 1, Mohamed M. Mire 1, Gabriel Núñez 1, Nicholas W. Lukacs 1,3 and Wendy Fonseca 1,* 1 Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] (C.-A.M.); [email protected] (A.J.D.); [email protected] (A.J.R.); [email protected] (M.M.M.); [email protected] (G.N.); [email protected] (N.W.L.) 2 Department of Internal Medicine, Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] 3 Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI 48109, USA * Correspondence: [email protected] Abstract: Respiratory syncytial virus (RSV) infects most infants by two years of age. It can cause severe disease leading to an increased risk of developing asthma later in life. Previously, our group has shown that RSV infection in mice and infants promotes IL-1β production. Here, we characterized the role of NLRP3-Inflammasome activation during RSV infection in adult mice and neonates. We observed that the inhibition of NLRP3 activation using the small molecule inhibitor, MCC950, or in Citation: Malinczak, C.-A.; Schuler, genetically modified NLRP3 knockout (Nlrp3−/−) mice during in vivo RSV infection led to decreased C.F.; Duran, A.J.; Rasky, A.J.; Mire, lung immunopathology along with a reduced expression of the mucus-associated genes and reduced M.M.; Núñez, G.; Lukacs, N.W.; production of innate cytokines (IL-1β, IL-33 and CCL2) linked to severe RSV disease while leading to Fonseca, W. -
Nicotine Induces Polyspermy in Sea Urchin Eggs Through a Non-Cholinergic Pathway Modulating Actin Dynamics
cells Article Nicotine Induces Polyspermy in Sea Urchin Eggs through a Non-Cholinergic Pathway Modulating Actin Dynamics 1,2 1, 2 1, Nunzia Limatola , Filip Vasilev y, Luigia Santella and Jong Tai Chun * 1 Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, I-80121 Napoli, Italy; [email protected] (N.L.); [email protected] (F.V.) 2 Department of Research Infrastructures for Marine Biological Resources, Stazione Zoologica Anton Dohrn, I-80121 Napoli, Italy; [email protected] * Correspondence: [email protected] Current address: Centre de Recherche du Centre Hospitalier de l’Université de Montreal (CRCHUM) y Montreal, QC H2X 0A9, Canada. Received: 8 November 2019; Accepted: 21 December 2019; Published: 25 December 2019 Abstract: While alkaloids often exert unique pharmacological effects on animal cells, exposure of sea urchin eggs to nicotine causes polyspermy at fertilization in a dose-dependent manner. Here, we studied molecular mechanisms underlying the phenomenon. Although nicotine is an agonist of ionotropic acetylcholine receptors, we found that nicotine-induced polyspermy was neither mimicked by acetylcholine and carbachol nor inhibited by specific antagonists of nicotinic acetylcholine receptors. Unlike acetylcholine and carbachol, nicotine uniquely induced drastic rearrangement of egg cortical microfilaments in a dose-dependent way. Such cytoskeletal changes appeared to render the eggs more receptive to sperm, as judged by the significant alleviation of polyspermy by latrunculin-A and mycalolide-B. In addition, our fluorimetric assay provided the first evidence that nicotine directly accelerates polymerization kinetics of G-actin and attenuates depolymerization of preassembled F-actin. Furthermore, nicotine inhibited cofilin-induced disassembly of F-actin. -
Inflammasome Regulation: Therapeutic Potential For
molecules Review Inflammasome Regulation: Therapeutic Potential for Inflammatory Bowel Disease Qiuyun Xu 1, Xiaorong Zhou 1 , Warren Strober 2,* and Liming Mao 1,3,* 1 Department of Immunology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226019, China; [email protected] (Q.X.); [email protected] (X.Z.) 2 Mucosal Immunity Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA 3 Basic Medical Research Center, School of Medicine, Nantong University, Nantong 226019, China * Correspondence: [email protected] (W.S.); [email protected] (L.M.) Abstract: Inflammasomes are multiprotein complexes formed to regulate the maturation of pro- inflammatory caspases, in response to intracellular or extracellular stimulants. Accumulating studies showed that the inflammasomes are implicated in the pathogenesis of inflammatory bowel disease (IBD), although their activation is not a decisive factor for the development of IBD. Inflammasomes and related cytokines play an important role in the maintenance of gut immune homeostasis, while its overactivation might induce excess immune responses and consequently cause tissue damage in the gut. Emerging studies provide evidence that some genetic abnormalities might induce enhanced NLRP3 inflammasome activation and cause colitis. In these cases, the colonic inflammation can be ameliorated by blocking NLRP3 activation or its downstream cytokine IL-1β. A number of natural products were shown to play a role in preventing colon inflammation in various experimental colitis models. On the other hand, lack of inflammasome function also causes intestinal abnormalities. Thus, an appropriate regulation of inflammasomes might be a promising therapeutic strategy for IBD Citation: Xu, Q.; Zhou, X.; Strober, intervention. -
J.M. Davis and L. Ramakrishnan. 2009. the Role of the Granuloma In
The Role of the Granuloma in Expansion and Dissemination of Early Tuberculous Infection J. Muse Davis1 and Lalita Ramakrishnan2,* 1Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA 30322, USA 2Departments of Microbiology, Medicine, and Immunology, University of Washington, Seattle, WA 98195, USA *Correspondence: [email protected] DOI 10.1016/j.cell.2008.11.014 SUMMARY and plateaus coincident with the development of adaptive immu- nity (North and Jung, 2004; Swaim et al., 2006). Hence, accord- Granulomas, organized aggregates of immune cells, ing to the classical model, granuloma formation requires adap- form in response to persistent stimuli and are hall- tive immunity and is critical for restricting bacterial expansion marks of tuberculosis. Tuberculous granulomas (Andersen, 1997; Saunders and Cooper, 2000). have long been considered host-protective struc- Studies in transparent zebrafish embryos infected with Myco- tures formed to contain infection. However, work in bacterium marinum (Mm), a system which recapitulates the zebrafish infected with Mycobacterium marinum earliest stages of tuberculosis (Clay et al., 2008; Dannenberg, 1993; Lesley and Ramakrishnan, 2008; Stamm and Brown, suggests that granulomas contribute to early bacte- 2004; Tobin and Ramakrishnan, 2008), refute the classical model rial growth. Here we use quantitative intravital micros- of granuloma initiation as a host-protective event in fundamental copy to reveal distinct steps of granuloma formation ways. First, epithelioid granulomas are found to form within days and assess their consequence for infection. Intracel- of infection, well before adaptive immunity is present (Davis lular mycobacteria use the ESX-1/RD1 virulence locus et al., 2002). Second, granuloma formation coincides with the to induce recruitment of new macrophages to, and accelerated bacterial expansion widely thought to precede it their rapid movement within, nascent granulomas. -
Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases
Mar. Drugs 2014, 12, 2539-2589; doi:10.3390/md12052539 OPEN ACCESS marine drugs ISSN 1660–3397 www.mdpi.com/journal/marinedrugs Review Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases Clara Grosso 1, Patrícia Valentão 1, Federico Ferreres 2 and Paula B. Andrade 1,* 1 REQUIMTE/Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal; E-Mails: [email protected] (C.G.); [email protected] (P.V.) 2 Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, Campus University Espinardo, Murcia 30100, Spain; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +351-22042-8654; Fax: +351-22609-3390. Received: 30 January 2014; in revised form: 10 April 2014 / Accepted: 16 April 2014 / Published: 2 May 2014 Abstract: Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted. Keywords: aragonite; conotoxins; neurodegeneration; neuroinflammation; Aβ peptide; tau hyperphosphorylation; protein kinases; receptors; voltage-dependent ion channels; cyclooxygenases Mar. -
Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis
Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis Alf Kastbom, Lisbeth Ärlestig, and Solbritt Rantapää-Dahlqvist ABSTRACT. Objective. Inflammasomes are intracellular protein complexes important for the production of pro- inflammatory cytokines. Studies have suggested that the NLRP3 inflammasome influences both the severity of rheumatoid arthritis (RA) and development of atherosclerosis. Therefore, we investigated whether functional genetic variants related to the NLRP3 inflammasome influence the risk of cardio- vascular (CV) disease (CVD) in patients with RA. Methods. The incidence of CVD was assessed in 522 patients with established RA by a retrospective survey of medical records in combination with a 6-year prospective followup. NLRP3-Q705K and CARD8-C10X genotypes were analyzed in relation to CVD by logistic regression, adjusting for tradi- tional risk factors, antirheumatic treatment, and age at the onset of RA. Results. Carriage of the NLRP3-Q705K minor allele was associated with an increased risk of stroke/transient ischemic attack (TIA; OR 2.01, 95% CI 1.0–4.1, p = 0.05), while CARD8-C10X was not associated with any type of CV event. Patients with ≥ 1 variant allele in both polymorphisms had an increased risk of CVD when compared with patients without variant alleles present in both polymor- phisms (adjusted OR 3.05, 95% CI 1.42–6.54, p = 0.004). Stratification showed that this risk was confined to stroke/TIA (adjusted OR 5.09, 95% CI 2.27–11.44, p < 0.0001) and not to myocardial infarction (MI)/angina pectoris (adjusted OR 1.58, 95% CI 0.67–3.73). -
Fungi.Mycotoxins.Pdf
Fungi: Mycotoxin: Acremonium crotocinigenum Crotocin Aspergillus favus Alfatoxin B, cyclopiazonic acid Aspergillus fumigatus Fumagilin, gliotoxin Aspergillus carneus Critrinin Aspergillus clavatus Cytochalasin, patulin Aspergillus Parasiticus Alfatoxin B Aspergillus nomius Alfatoxin B Aspergillus niger Ochratoxin A, malformin, oxalicacid Aspergillus nidulans Sterigmatocystin Aspergillus ochraceus Ochratoxin A, penicillic acid Aspergillus versicolor Sterigmatocystin, 5 ethoxysterigmatocystin Aspergillus ustus Ausdiol, austamide, austocystin, brevianamide Aspergillus terreus Citreoviridin Alternaria Alternariol, altertoxin, altenuene, altenusin, tenuazonic acid Arthrinium Nitropropionic acid Bioploaris Cytochalasin, sporidesmin, sterigmatocystin Chaetomium Chaetoglobosin A,B,C. Sterigmatocystin Cladosporium Cladosporic acid Clavipes purpurea Ergotism Cylindrocorpon Trichothecene Diplodia Diplodiatoxin Fusarium Trichothecene, zearalenone Fusarium moniliforme Fumonisins Emericella nidulans Sterigmatocystin Gliocladium Gliotoxin Memnoniella Griseofulvin, dechlorogriseofulvin, epidecholorgriseofulvin, trichodermin, trichodermol Myrothecium Trichothecene Paecilomyces Patulin, viriditoxin Penicillium aurantiocandidum Penicillic acid Penicillium aurantiogriseum Penicillic acid Penicillium brasalianum Penicillic acid Penicillium brevicompactum Mycophenolic acid Penicillium camemberti Cyclopiazonic acid Penicillium carneum Mycophenolic acid, Roquefortine C Penicillium crateriforme Rubratoxin Penicillium citrinum Citrinin Penicillium commune Cyclopiazonic -
NLRP3 Inflammasome at the Interface of Inflammation, Endothelial
cells Review NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes Ilona M. Gora *, Anna Ciechanowska and Piotr Ladyzynski Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Ks. Trojdena 4, 02-109 Warsaw, Poland; [email protected] (A.C.); [email protected] (P.L.) * Correspondence: [email protected] Abstract: Type 2 diabetes mellitus (T2DM), accounting for 90–95% cases of diabetes, is characterized by chronic inflammation. The mechanisms that control inflammation activation in T2DM are largely unexplored. Inflammasomes represent significant sensors mediating innate immune responses. The aim of this work is to present a review of links between the NLRP3 inflammasome, endothelial dys- function, and T2DM. The NLRP3 inflammasome activates caspase-1, which leads to the maturation of pro-inflammatory cytokines interleukin 1β and interleukin 18. In this review, we characterize the structure and functions of NLRP3 inflammasome as well as the most important mechanisms and molecules engaged in its activation. We present evidence of the importance of the endothelial dysfunction as the first key step to activating the inflammasome, which suggests that suppressing the NLRP3 inflammasome could be a new approach in depletion hyperglycemic toxicity and in averting the onset of vascular complications in T2DM. We also demonstrate reports showing that the expression of a few microRNAs that are also known to be involved in either NLRP3 inflammasome activation or endothelial dysfunction is deregulated in T2DM. Collectively, this evidence suggests that T2DM is an inflammatory disease stimulated by pro-inflammatory cytokines. Finally, studies revealing the role of glucose concentration in the activation of NLRP3 inflammasome are analyzed. -
The Molecular Links Between Cell Death and Inflammasome
cells Review The Molecular Links between Cell Death and Inflammasome Kwang-Ho Lee 1,2 and Tae-Bong Kang 1,2,* 1 Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Korea 2 Research Institute of Inflammatory Diseases, Konkuk University, Chungju 27478, Korea * Correspondence: [email protected]; Tel.: +82-43-840-3904; Fax: +82-43-852-3616 Received: 30 July 2019; Accepted: 9 September 2019; Published: 10 September 2019 Abstract: Programmed cell death pathways and inflammasome activation pathways can be genetically and functionally separated. Inflammasomes are specialized protein complexes that process pro-inflammatory cytokines, interleukin-1β (IL-1β), and IL-18 to bioactive forms for protection from a wide range of pathogens, as well as environmental and host-derived danger molecules. Programmed cell death has been extensively studied, and its role in the development, homeostasis, and control of infection and danger is widely appreciated. Apoptosis and the recently recognized necroptosis are the best-characterized forms of programmed death, and the interplay between them through death receptor signaling is also being studied. Moreover, growing evidence suggests that many of the signaling molecules known to regulate programmed cell death can also modulate inflammasome activation in a cell-intrinsic manner. Therefore, in this review, we will discuss the current knowledge concerning the role of the signaling molecules originally associated with programmed cell death in the activation of inflammasome and IL-1β processing. Keywords: inflammasome; apoptosis; necroptosis; programmed cell death; Caspase-8; RIPK1/3; MLKL; PGAM5; DRP1 1. Introduction Homeostasis is a principle property of living organisms and it is maintained at the systemic, tissue, and cellular levels through the homeostatic control system. -
Eosinophil Functions Mitogen-Activated Protein Kinase In
The Differential Role of Extracellular Signal-Regulated Kinases and p38 Mitogen-Activated Protein Kinase in Eosinophil Functions This information is current as of September 30, 2021. Tetsuya Adachi, Barun K. Choudhury, Susan Stafford, Sanjiv Sur and Rafeul Alam J Immunol 2000; 165:2198-2204; ; doi: 10.4049/jimmunol.165.4.2198 http://www.jimmunol.org/content/165/4/2198 Downloaded from References This article cites 57 articles, 38 of which you can access for free at: http://www.jimmunol.org/content/165/4/2198.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 30, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Differential Role of Extracellular Signal-Regulated Kinases and p38 Mitogen-Activated Protein Kinase in Eosinophil Functions1 Tetsuya Adachi, Barun K. Choudhury, Susan Stafford, Sanjiv Sur, and Rafeul Alam2 The activation of eosinophils by cytokines is a major event in the pathogenesis of allergic diseases.