DOCSLIB.ORG

Cells to Induce Survival and Activation of Mast Leukotriene Synthetic And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cells to Induce Survival and Activation of Mast Leukotriene Synthetic And P2Y6 Receptors Require an Intact Cysteinyl Leukotriene Synthetic and Signaling System to Induce Survival and Activation of Mast Cells This information is current as of September 30, 2021. Yongfeng Jiang, Laura Borrelli, Brian J. Bacskai, Yoshihide Kanaoka and Joshua A. Boyce J Immunol 2009; 182:1129-1137; ; doi: 10.4049/jimmunol.182.2.1129 http://www.jimmunol.org/content/182/2/1129 Downloaded from References This article cites 58 articles, 31 of which you can access for free at: http://www.jimmunol.org/content/182/2/1129.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 © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology P2Y6 Receptors Require an Intact Cysteinyl Leukotriene Synthetic and Signaling System to Induce Survival and Activation of Mast Cells1 Yongfeng Jiang,* Laura Borrelli,‡ Brian J. Bacskai,‡ Yoshihide Kanaoka,* and Joshua A. Boyce2*† Cysteinyl leukotrienes (cys-LTs) induce inflammatory responses through type 1 (CysLT1R) and type 2 (CysLT2R) cys-LT recep- tors and activate mast cells in vitro. We previously demonstrated that cys-LTs cross-desensitized IL-4-primed primary human mast cells (hMCs) to stimulation with the nucleotide uridine diphosphate (UDP). We now report that hMCs, mouse bone marrow- derived mast cells (mBMMCs), and the human MC line LAD2 all express UDP-selective P2Y6 receptors that cooperate with CysLT1R to promote cell survival and chemokine generation by a pathway involving reciprocal ligand-mediated cross-talk. Downloaded from Leukotriene (LT) D4, the most potent CysLT1R ligand, and UDP both induced phosphorylation of ERK and prolonged the survival of cytokine-starved hMCs and mBMMCs. ERK activation and cytoprotection in response to either ligand were attenuated by treatment of the cells with a selective P2Y6 receptor antagonist (MRS2578), which did not interfere with signaling through recombinant CysLT1R. Surprisingly, both UDP and LTD4-mediated ERK activation and cytoprotection were absent in mBMMCs lacking CysLT1R and the biosynthetic enzyme LTC4 synthase, implying a requirement for a cys-LT-mediated autocrine loop. In ␤ http://www.jimmunol.org/ IL-4-primed LAD2 cells, LTD4 induced the generation of MIP-1 , a response blocked by short hairpin RNA-mediated knockdown of CysLT1R or P2Y6 receptors, but not of CysLT2R. Thus, CysLT1R and P2Y6 receptors, which are coexpressed on many cell types of innate immunity, reciprocally amplify one another’s function in mast cells through endogenous ligands. The Journal of Immunology, 2009, 182: 1129–1137. 3 ϭ Ͼ eukotriene (LT) C4, LTD4, and LTE4, collectively whereas CysLT2R binds LTC4 LTD4 LTE4 (6). CysLT1Ris known as the cysteinyl LTs (cys-LTs), are arachidonic expressed by airway and vascular smooth muscle, as well as by L acid-derived inflammatory lipid mediators generated by leukocytes such as neutrophils and eosinophils, macrophages mast cells (MCs), eosinophils, basophils, and alveolar macro- (5, 7) and MCs (8). CysLT2R is expressed by endothelial and by guest on September 30, 2021 phages (reviewed in Ref. 1). They potently contract smooth muscle epithelial cells, heart, brain, adrenal medulla, certain leuko- in humans (2) and regulate vascular responses to passive anaphy- cytes, macrophages, and mast cells (MCs) (6). In accord with laxis and experimental peritonitis in mice (3). cys-LTs are estab- their incompletely overlapping distributions, each receptor for lished mediators of asthma (4). Two G protein-coupled receptors cys-LTs has distinct functions. For example, the vascular (GPCRs) for cys-LTs, the type 1 (CysLT1R) and type 2 (CysLT2R) smooth muscle contractile effects of cys-LTs depend either on receptors, mediate the effects of cys-LTs in vivo (5, 6). CysLT1R CysLT R solely or on both receptors, contingent on the tissue Ͼ Ͼ 1 binds cys-LTs with a rank order of LTD4 LTC4 LTE4 (5), location (9). Whereas CysLT2R is obligate for pulmonary fi- brosis induced by bleomycin, CysLT1R is protective in this cir- † *Department of Medicine and Department of Pediatrics, Harvard Medical School cumstance (9). On MCs, CysLT1R and CysLT2R heterodimer- and Division of Rheumatology, Immunology and Allergy, Brigham and Women’s ize and the latter receptor acts as a negative regulator of the Hospital; and ‡Department of Neurology, MassGeneral Institute for Neurodegenera- tive Disease, Massachusetts General Hospital, Boston, MA 02115 former’s actions (10). Ͼ Received for publication September 26, 2008. Accepted for publication November Among the 400 GPCRs encoded by mammalian genomes, 5, 2008. the closest homologs of the cys-LT receptors are the purinergic The costs of publication of this article were defrayed in part by the payment of page (P2Y) receptors for extracellular nucleotides. Eight such charges. This article must therefore be hereby marked advertisement in accordance GPCRs (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, with 18 U.S.C. Section 1734 solely to indicate this fact. and P2Y14) have confirmed nucleotide specificity (reviewed in 1 This work was supported by National Institutes of Health Grants AI-48802, AI- 52353, AI-31599, HL-36110, and EB-00768 and by grants from the Charles Dana Ref. 11). Some P2Y receptors are expressed in the CNS and Foundation and the Vinik Family Fund for Research in Allergic Diseases. others are expressed by vascular structures, epithelial cells, 2 Address correspondence and reprint requests to Dr. Joshua A. Boyce, Brigham and and hematopoietic cells. Cellular damage due to vascular injury Women’s Hospital, Harvard Medical School, One Jimmy Fund Way, Smith Building and shear stress causes the release of large amounts of nucle- Room 626, Boston, MA 02115. E-mail: [email protected] otides, which can also be released in a regulated fashion by 3 Abbreviations used in this paper: LT, leukotriene; cys-LT, cysteinyl LT; CysLT1R, ␧ activation of secretory cell types such as MCs (12) or platelets. type 1 receptor for cys-LT; CysLT2R, type 2 receptor for cys-LT; Fc RI, high-affinity Fc receptor for IgE; FLAP, 5-lipoxygenase activating protein; GPCR, G protein- Thus, during tissue injury or inflammatory responses, extracel- coupled receptor; hMC, cord blood-derived human MC; LTC4S, LTC4 synthase; MC, lular concentrations of nucleotides can reach micromolar con- mast cell; P2Y, purinergic; SCF, stem cell factor; shRNA, short hairpin RNA; MC, mast cell; UDP, uridine diphosphate; mBMMC, mouse bone marrow-derived centrations, with even higher local concentrations at cell-cell MC; FLIM, fluorescence lifetime imaging microscopy; MFI, mean fluorescence in- junctions (11). In these contexts, P2Y receptors can function as tensity; FRET, fluorescence resonance energy transfer; CHO, Chinese hamster ovary. “danger sensors,” activating pain fibers (13), and regulating Copyright © 2009 by The American Association of Immunologists, Inc. 0022-1767/09/$2.00 platelet aggregation (14, 15). P2Y receptors can also induce www.jimmunol.org 1130 cys-LT-UDP INTERACTIONS migration and phagocytic function of microglia (16, 17) and Materials and Methods cause the migration of monocytes (18) and activation of mac- Reagents rophages (19), MCs (20), and myeloid dendritic cells (21). Al- LTD4 and MK571 were purchased from Cayman Chemical. Polyclonal though most P2Y receptors preferentially recognize adenine nu- anti-peptide Abs were raised against conserved sequences of human and cleotides (ATP or ADP), some recognize uracil nucleotides. mouse CysLT1R (RB34, against extracellular domain 3), CysLT2R (RB19, The human P2Y4 receptor binds UTP and the P2Y14 receptor against extracellular domain 2), and the P2Y6 receptor (RB165, against the recognizes the uridine diphosphate (UDP) metabolite UDP-glu- second intracellular loop of the human P2Y6 receptor CQRYLGICH PLAPWHKRGG by Orbigen). An additional Ab against the C terminus of cose (21). A recently deorphanized GPCR, GPR17, is expressed the human CysLT1R (Cayman Chemical) was used for the fluorescence ␤ in the CNS and confers calcium signals in response to uracil- lifetime imaging microscopy (FLIM) assays. Monoclonal anti- 1 and poly- ␣ containing nucleotides and to LTD4 when expressed by trans- clonal anti- 4 integrin Abs were purchased from BD Pharmingen. Alexa fection into an astrocyte cell line (22). The P2Y6 receptor is the Fluor 488-conjugated goat anti-rabbit IgG and Cy3-conjugated donkey anti- mouse IgG were purchased from Invitrogen. Alexa Fluor 488 and Cy3 only known UDP-specific GPCR and is strongly expressed by (Amersham Biosciences) were used for direct labeling according to the vascular smooth muscle (23) and the spleen (24). Many cells of manufacturer’s protocols. Recombinant human and mouse cytokines were myelomonocytic origin (osteoclasts (25), microglia (17),
Load more

Recommended publications
  • Chemical Tools for Studying Lipid-Binding Class a G Protein–Coupled Receptors
    1521-0081/69/3/316–353$25.00 https://doi.org/10.1124/pr.116.013243 PHARMACOLOGICAL REVIEWS Pharmacol Rev 69:316–353, July 2017 Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: STEPHEN P. H. ALEXANDER Chemical Tools for Studying Lipid-Binding Class A G Protein–Coupled Receptors Anna Cooper, Sameek Singh, Sarah Hook, Joel D. A. Tyndall, and Andrea J. Vernall School of Pharmacy, University of Otago, Dunedin, New Zealand Abstract. ....................................................................................317 I. Introduction. ..............................................................................317 A. Cannabinoid Receptor . ..................................................................317 1. Ligand Classes. ......................................................................318 B. Free Fatty Acid Receptor ................................................................320 1. Ligand Classes. ......................................................................320 C. Lysophospholipid Receptors. ............................................................321 1. Ligand Classes. ......................................................................321 D. Prostanoid Receptor . ..................................................................321 Downloaded from 1. Ligand Classes. ......................................................................322 E. Leukotriene Receptor . ..................................................................322 1. Ligand Classes. ......................................................................322
    [Show full text]
  • System, Method and Software for Calculation of a Cannabis Drug Efficiency Index for the Reduction of Inflammation
    International Journal of Molecular Sciences Article System, Method and Software for Calculation of a Cannabis Drug Efficiency Index for the Reduction of Inflammation Nicolas Borisov 1,† , Yaroslav Ilnytskyy 2,3,†, Boseon Byeon 2,3,4,†, Olga Kovalchuk 2,3 and Igor Kovalchuk 2,3,* 1 Moscow Institute of Physics and Technology, 9 Institutsky lane, Dolgoprudny, Moscow Region 141701, Russia; [email protected] 2 Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; [email protected] (Y.I.); [email protected] (B.B.); [email protected] (O.K.) 3 Pathway Rx., 16 Sandstone Rd. S., Lethbridge, AB T1K 7X8, Canada 4 Biomedical and Health Informatics, Computer Science Department, State University of New York, 2 S Clinton St, Syracuse, NY 13202, USA * Correspondence: [email protected] † First three authors contributed equally to this research. Abstract: There are many varieties of Cannabis sativa that differ from each other by composition of cannabinoids, terpenes and other molecules. The medicinal properties of these cultivars are often very different, with some being more efficient than others. This report describes the development of a method and software for the analysis of the efficiency of various cannabis extracts to detect the anti-inflammatory properties of the various cannabis extracts. The method uses high-throughput gene expression profiling data but can potentially use other omics data as well. According to the signaling pathway topology, the gene expression profiles are convoluted into the signaling pathway activities using a signaling pathway impact analysis (SPIA) method. The method was tested by inducing inflammation in human 3D epithelial tissues, including intestine, oral and skin, and then exposing these tissues to various extracts and then performing transcriptome analysis.
    [Show full text]
  • Regulation of Immune Cells by Eicosanoid Receptors
    Regulation of Immune Cells by Eicosanoid Receptors The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Kim, Nancy D., and Andrew D. Luster. 2007. “Regulation of Immune Cells by Eicosanoid Receptors.” The Scientific World Journal 7 (1): 1307-1328. doi:10.1100/tsw.2007.181. http://dx.doi.org/10.1100/ tsw.2007.181. Published Version doi:10.1100/tsw.2007.181 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:37298366 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Review Article Special Issue: Eicosanoid Receptors and Inflammation TheScientificWorldJOURNAL (2007) 7, 1307–1328 ISSN 1537-744X; DOI 10.1100/tsw.2007.181 Regulation of Immune Cells by Eicosanoid Receptors Nancy D. Kim and Andrew D. Luster* Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston E-mail: [email protected] Received March 13, 2007; Revised June 14, 2007; Accepted July 2, 2007; Published September 1, 2007 Eicosanoids are potent, bioactive, lipid mediators that regulate important components of the immune response, including defense against infection, ischemia, and injury, as well as instigating and perpetuating autoimmune and inflammatory conditions. Although these lipids have numerous effects on diverse cell types and organs, a greater understanding of their specific effects on key players of the immune system has been gained in recent years through the characterization of individual eicosanoid receptors, the identification and development of specific receptor agonists and inhibitors, and the generation of mice genetically deficient in various eicosanoid receptors.
    [Show full text]
  • Cytogenetic Analysis of a Pseudoangiomatous Pleomorphic/Spindle Cell Lipoma
    ANTICANCER RESEARCH 37 : 2219-2223 (2017) doi:10.21873/anticanres.11557 Cytogenetic Analysis of a Pseudoangiomatous Pleomorphic/Spindle Cell Lipoma IOANNIS PANAGOPOULOS 1, LUDMILA GORUNOVA 1, INGVILD LOBMAIER 2, HEGE KILEN ANDERSEN 1, BODIL BJERKEHAGEN 2 and SVERRE HEIM 1,3 1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; 2Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; 3Faculty of Medicine, University of Oslo, Oslo, Norway Abstract. Background: Pseudoangiomatous pleomorphic/ appearance’ (1). To date, only 20 patients have been described spindle cell lipoma is a rare subtype of pleomorphic/spindle in the literature with this diagnosis, 15 of whom were males cell lipoma. Only approximately 20 such tumors have been (1-10). The pseudoangiomatous pleomorphic/spindle cell described. Genetic information on pseudoangiomatous lipomas were mostly found in the neck (seven patients) and pleomorphic/spindle cell lipoma is restricted to a single case shoulders (four patients), but have also been seen in the in which deletion of the forkhead box O1 (FOXO1) gene was cheek, chest, chin, elbow, finger, subscapular region, and found, using fluorescence in situ hybridization (FISH). thumb. Genetic information on pseudoangiomatous Materials and Methods: G-banding and FISH analyses were pleomorphic/ spindle cell lipoma is restricted to one case only performed on a pseudoangiomatous pleomorphic/spindle cell (8) in which fluorescence in situ hybridization (FISH) with a lipoma. Results: G-banding of tumor cells showed complex probe for the forkhead box O1 ( FOXO1 ) gene, which maps karyotypic changes including loss of chromosome 13. FISH to chromosome sub-band 13q14.11, showed a signal pattern analysis revealed that the deleted region contained the RB1 indicating monoallelic loss of the gene in 57% of the gene (13q14.2) and the part of chromosome arm 13q (q14.2- examined cells.
    [Show full text]
  • Type-2 CD8+ T Lymphocytes Responsive to PGD2 and LTE4 In
    bioRxiv preprint doi: https://doi.org/10.1101/247171; this version posted January 12, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. + Type-2 CD8 T lymphocytes responsive to PGD2 and LTE4 in severe eosinophilic asthma Bart Hilvering,1† Timothy SC Hinks,1,2† Linda Stöger,1,3† Emanuele Marchi,4† Maryam Salimi,5 Rahul Shrimanker,1 Wei Liu,1 Wentao Chen,1 Jian Luo,1 Simei Go,1 Timothy Powell,1 Jennifer Cane,1 Samantha Thulborn,1 Ayako Kurioka,4 Tianqi Leng,4 Jamie Matthews,4 Clare Connolly,1 Catherine Borg,1 Mona Bafadhel,1 Christian B Willberg,3,4 Adaikalavan Ramasamy,6 Ratko Djukanović,2,7 Graham Ogg,5 Ian D Pavord,1‡ Paul Klenerman,4‡ Luzheng Xue1,3‡* 1Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. 2Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton University Hospital, Southampton, UK. 3Oxford Biomedical Research Centre, Core Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. 4Translational Gastroenterology Unit and Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, UK. 5MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. 6Transcriptomic Core Facility, The Jenner Institute, University of Oxford, UK. 7NIHR Southampton Respiratory Biomedical Research Unit, Southampton University Hospital, Southampton, UK. † These authors are co-first authors. ‡ These authors contributed equally as joint senior authors.
    [Show full text]
  • Emerging Role of Cysteinyl Leukotrienes in Cancer
    Emerging role of cysteinyl leukotrienes in cancer Lou Saier1 and Olivier Peyruchaud2 1INSERM U1033 2INSERM September 11, 2020 Abstract Cysteinyl leukotrienes (CysLTs) are inflammatory lipid mediators that play a central role in the pathophysiology of several inflammatory diseases. Recently, there has been an increased interest in determining how these lipid mediators orchestrate tumor development and metastasis through promoting a pro-tumoral microenvironment. Upregulation of CysLTs receptors and CysLTs production is found in a number of cancers and has been associated with increased tumorigenesis. Understanding the molecular mechanisms underlying the role of CysLTs and their receptors in cancer progression will help investigate the potential of targeting CysLTs signaling for anti-cancer therapy. This review gives an overview of the biological effects of CysLTs and their receptors, along with current knowledge of their regulation and expression. It also provides a recent update on the molecular mechanisms that have been postulated to explain their role in tumorigenesis and on the potential of anti-CysLTs in the treatment of cancer. KEYWORDS Cysteinyl leukotrienes, inflammation, cancer, metastasis INTRODUCTION Cysteinyl leukotrienes (CysLTs) are one of the major constituents of the eicosanoid family of bioactive in- flammatory lipid-mediators. They are rapidly generated at the site of inflammation in response to immuno- logical and nonimmunological stimuli following the release of arachidonic acid through the 5-lipoxygenase (5-LOX) pathway (Figure 1A). The term CysLTs includes leukotriene C4(LTC4), leukotriene D4(LTD4), and leukotriene E4(LTE4); they are structurally different from leukotriene A4 (LTA4) and leukotriene B4 (LTB4), which are commonly known as leukotrienes (LTs). Leukotrienes exhibit diverse biological effects such as contraction of bronchial smooth muscle, stimulation of vascular permeability, and attraction and activation of leukocytes (Hammarstr¨om,1983).
    [Show full text]
  • 2 Production in Response to Prostaglandin D for Exaggerated
    Leukotriene E4 Activates Human Th2 Cells for Exaggerated Proinflammatory Cytokine Production in Response to Prostaglandin D2 This information is current as Luzheng Xue, Anna Barrow, Vicki M. Fleming, Michael G. of September 27, 2021. Hunter, Graham Ogg, Paul Klenerman and Roy Pettipher J Immunol 2012; 188:694-702; Prepublished online 14 December 2011; doi: 10.4049/jimmunol.1102474 http://www.jimmunol.org/content/188/2/694 Downloaded from References This article cites 59 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/188/2/694.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 27, 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 © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Leukotriene E4 Activates Human Th2 Cells for Exaggerated Proinflammatory Cytokine Production in Response to Prostaglandin D2 Luzheng Xue,* Anna Barrow,† Vicki M. Fleming,‡ Michael G. Hunter,† Graham Ogg,*,x Paul Klenerman,*,‡ and Roy Pettipher† PGD2 exerts a number of proinflammatory responses through a high-affinity interaction with chemoattractant receptor- homologous molecule expressed on Th2 cells (CRTH2) and has been detected at high concentrations at sites of allergic inflam- mation.
    [Show full text]
  • Antileukotrienes in Upper Airway Inflammatory Diseases
    Curr Allergy Asthma Rep (2015) 15:64 DOI 10.1007/s11882-015-0564-7 RHINOSINUSITIS (J MULLOL, SECTION EDITOR) Antileukotrienes in Upper Airway Inflammatory Diseases Cemal Cingi1,5 & Nuray Bayar Muluk2 & Kagan Ipci3 & Ethem Şahin4 # Springer Science+Business Media New York 2015 Abstract Leukotrienes (LTs) are a family of inflammatory zileuton, ZD2138, Bay X 1005, and MK-0591). CysLTs have mediators including LTA4,LTB4,LTC4,LTD4, and LTE4. important proinflammatory and profibrotic effects that con- By competitive binding to the cysteinyl LT1 (CysLT1)recep- tribute to the extensive hyperplastic rhinosinusitis and nasal tor, LT receptor antagonist drugs, such as montelukast, polyposis (NP) that characterise these disorders. Patients who zafirlukast, and pranlukast, block the effects of CysLTs, im- receive zafirlukast or zileuton tend to show objective improve- proving the symptoms of some chronic respiratory diseases, ments in, or at least stabilisation of, NP.Montelukast treatment particularly bronchial asthma and allergic rhinitis. We may lead to clinical subjective improvement in NP. reviewed the efficacy of antileukotrienes in upper airway in- Montelukast treatment after sinus surgery can lead to a signif- flammatory diseases. An update on the use of antileukotrienes icant reduction in eosinophilic cationic protein levels in se- in upper airway diseases in children and adults is presented rum, with a beneficial effect on nasal and pulmonary symp- with a detailed literature survey. Data on LTs, antileukotrienes, toms and less impact in NP. Combined inhaled corticosteroids and antileukotrienes in chronic rhinosinusitis and nasal and long-acting β-agonists treatments are most effective for polyps, asthma, and allergic rhinitis are presented. preventing exacerbations among paediatric asthma patients.
    [Show full text]
  • UDP-Glucose and P2Y14 Receptor Amplify Allergen-Induced Airway Eosinophilia
    UDP-glucose and P2Y14 receptor amplify allergen-induced airway eosinophilia Tadeusz P. Karcz, … , Kenneth A. Jacobson, Donald N. Cook J Clin Invest. 2021;131(7):e140709. https://doi.org/10.1172/JCI140709. Research Article Inflammation Graphical abstract Find the latest version: https://jci.me/140709/pdf The Journal of Clinical Investigation UDP-glucose and P2Y14 receptor amplify allergen-induced airway eosinophilia Tadeusz P. Karcz,1 Gregory S. Whitehead,1 Keiko Nakano,1 Hideki Nakano,1 Sara A. Grimm,2 Jason G. Williams,3 Leesa J. Deterding,3 Kenneth A. Jacobson,4 and Donald N. Cook1 1Immunity, Inflammation and Disease Laboratory, 2Integrative Bioinformatics, 3Mass Spectrometry Research and Support Group, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA. 4Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA. Airway eosinophilia is a hallmark of allergic asthma and is associated with mucus production, airway hyperresponsiveness, and shortness of breath. Although glucocorticoids are widely used to treat asthma, their prolonged use is associated with several side effects. Furthermore, many individuals with eosinophilic asthma are resistant to glucocorticoid treatment, and they have an unmet need for novel therapies. Here, we show that UDP-glucose (UDP-G), a nucleotide sugar, is selectively released into the airways of allergen-sensitized mice upon their subsequent challenge with that same allergen. Mice lacking P2Y14R, the receptor for UDP-G, had decreased airway eosinophilia and airway hyperresponsiveness compared with wild- type mice in a protease-mediated model of asthma. P2Y14R was dispensable for allergic sensitization and for the production of type 2 cytokines in the lung after challenge.
    [Show full text]
  • The Cyslt2r Receptor Mediates Leukotriene C4-Driven Acute and Chronic Itch
    The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch Tiphaine Voisina, Caroline Pernerb, Marie-Angele Messoua, Stephanie Shiersc, Saltanat Ualiyevad,e, Yoshihide Kanaokad,e, Theodore J. Pricec, Caroline L. Sokolb, Lora G. Bankovad,e, K. Frank Austend,e,1, and Isaac M. Chiua,1 aDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115; bCenter for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; cCenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX 75080; dDivision of Allergy and Clinical Immunology, Jeff and Penny Vinik Center for Allergic Disease Research, Brigham & Women’s Hospital, Boston, MA 02115; and eDepartment of Medicine, Harvard Medical School, Boston, MA 02115 Contributed by K. Frank Austen, February 2, 2021 (sent for review October 26, 2020; reviewed by Diana M. Bautista and Bradley J. Undem) Acute and chronic itch are burdensome manifestations of skin during inflammation. The biosynthesis of LTs begins when arachi- pathologies including allergic skin diseases and atopic dermatitis, donic acid is liberated from membrane phospholipids and is con- but the underlying molecular mechanisms are not well understood. verted into LTA4 by the enzyme 5-lipoxygenase (5-LO) in the Cysteinyl leukotrienes (CysLTs), comprising LTC4,LTD4, and LTE4,are presence of the 5-LO–associated protein (FLAP; Fig. 1A). LTA4 produced by immune cells during type 2 inflammation. Here, we hydrolase processes LTA4 into LTB4, which binds to the LTB4 uncover a role for LTC4 and its signaling through the CysLT receptor receptors.
    [Show full text]
  • G Protein‐Coupled Receptors
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology (2019) 176, S21–S141 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors Stephen PH Alexander1 , Arthur Christopoulos2 , Anthony P Davenport3 , Eamonn Kelly4, Alistair Mathie5 , John A Peters6 , Emma L Veale5 ,JaneFArmstrong7 , Elena Faccenda7 ,SimonDHarding7 ,AdamJPawson7 , Joanna L Sharman7 , Christopher Southan7 , Jamie A Davies7 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia 3Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK 4School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 5Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 6Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 7Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website.
    [Show full text]
  • Leukotriene B4 Pathway Regulates the Fate of the Hematopoietic Stem Cells
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 37, No. 1, 45-50, February 2005 Leukotriene B4 pathway regulates the fate of the hematopoietic stem cells Jin Woong Chung1, Geun-Young Kim1, Introduction Yeung-Chul Mun2, Ji-Young Ahn2, 2 1,3 Hematopoietic stem cells (HSCs) have ability to self Chu-Myong Seong and Jae-Hong Kim renew while functionally repopulating the cells of the blood and lymph for the life of an individual. These 1School of Life Sciences and Biotechnology cells are thought to retain a high capacity for plasticity Korea University, Seoul 136-701, Korea that would contribute to their ability to differentiate into 2Department of Oncology/Hematology not only hematopoietic cells but also non-hemato- College of Medicine, Ewha Woman's University poietic tissues such as brain, heart, skeletal muscle, Seoul 158-056, Korea liver and endothelial cells, following injury or stress 3 (Heike et al., 2004). Such capacity of these cells Coressponding author: Tel, 82-2-3290-3452; gives rise to the hope that hematopoietic stem cells Fax, 82-2-3290-3960; E-mail, [email protected] may regenerate various damaged tissues. In that regard, ex vivo expansion of hematopoietic stem cells Accepted 31 January 2005 is a promising technology for many potential ap- plications from marrow reconstitution to gene therapy. Abbreviations: FL, Flt-3 ligand; HSC, hematopoietic stem cell; Despite of considerable progresses gained during the LTB4, leukotriene B4; RT-PCR, reverse transcription PCR; TPO, past ten years in understanding the biology of thrombopoietin; UCB, umbilical cord blood hematopoietic stem cells and its ex vivo expansion, the success was limited (Piacibello et al., 1997; Shih et al., 1999; Lewis et al., 2001).
    [Show full text]