DOCSLIB.ORG

TRP Channels As Drug Targets to Relieve Itch Zili Xie Washington University School of Medicine in St

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
TRP Channels As Drug Targets to Relieve Itch Zili Xie Washington University School of Medicine in St Washington University School of Medicine Digital Commons@Becker Open Access Publications 2018 TRP channels as drug targets to relieve itch Zili Xie Washington University School of Medicine in St. Louis Hongzhen Hu Washington University School of Medicine in St. Louis Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Xie, Zili and Hu, Hongzhen, ,"TRP channels as drug targets to relieve itch." Pharmaceuticals.11,4. 100. (2018). https://digitalcommons.wustl.edu/open_access_pubs/7299 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. pharmaceuticals Review TRP Channels as Drug Targets to Relieve Itch Zili Xie and Hongzhen Hu * Department of Anesthesiology, The Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA; [email protected] * Correspondence: [email protected]; Tel: +1-314-747-4317 Received: 4 September 2018; Accepted: 3 October 2018; Published: 6 October 2018 Abstract: Although acute itch has a protective role by removing irritants to avoid further damage, chronic itch is debilitating, significantly impacting quality of life. Over the past two decades, a considerable amount of stimulating research has been carried out to delineate mechanisms of itch at the molecular, cellular, and circuit levels. There is growing evidence that transient receptor potential (TRP) channels play important roles in itch signaling. The purpose of this review is to summarize our current knowledge about the role of TRP channels in the generation of itch under both physiological and pathological conditions, thereby identifying them as potential drug targets for effective anti-itch therapies. Keywords: TRP channels; itch; pain; TRPA1; TRPV1; TRPV3; TRPV4; TRPM8; TRPC4; agonists; antagonists 1. Introduction Itch, also known as pruritus, is an unpleasant sensation provoking the scratch reflex [1]. Itch is classified as acute or chronic, with the latter defined as pruritus lasting longer than six weeks [2]. Acute itch is often generated locally in the skin by pruritogens and the scratching behavior that is evoked has a protective role by removing irritants. Chronic itch, by contrast, may be maladaptive and leads to significant decrements in quality of life. It is associated with numerous conditions, including atopic eczema, psoriasis, urticaria, inflammatory skin diseases, chronic renal failure, cholestasis, lymphoma, and chronic liver diseases [3–6]. Chronic itch remains an unmet medical condition lacking universally effective treatments. Delineating itch mechanisms at the molecular, cellular, and circuit levels is critical to the development of new anti-itch therapeutic strategies. The transient receptor potential (TRP) channels comprise 28 members in mammals that can be divided into six subfamilies based on amino acid sequence homology, including TRPA, TRPC, TRPM, TRPML, TRPP, and TRPV [7]. TRP channels respond to a diverse array of thermal, chemical, and mechanical stimuli. They are implicated in many sensory functions including taste, smell, thermoception, touch, osmolarity, and pain [8–12]. In the past two decades, numerous studies have demonstrated that TRP channels are critically involved in itch sensation under both physiological and pathological conditions [13,14]. 2. Cellular Mechanisms of Itch Signaling in the Periphery Itch has long been considered a submodality of pain based on observations that local stimulation of the same skin sites at low intensities evokes itch, whereas high intensities cause pain [15]. Pain and itch are now clearly understood to be distinct sensory modalities [16–18]. Pruritogens evoke itch sensation by activating pruriceptors present on free nerve endings of cutaneous primary sensory neurons [19]. Primary sensory neurons are classified into four distinct types based on cell body size and axon myelination: (1) large-diameter, thickly myelinated proprioceptive neurons; (2) large-diameter, myelinated Aβ low-threshold mechanoreceptors which mediate touch; (3) medium-sized, lightly Pharmaceuticals 2018, 11, 100; doi:10.3390/ph11040100 www.mdpi.com/journal/pharmaceuticals Pharmaceuticals 2018, 11, x 2 of 21 distinct types based on cell body size and axon myelination: (1) large-diameter, thickly myelinated proprioceptive neurons; (2) large-diameter, myelinated Aβ low-threshold mechanoreceptors which mediate touch; (3) medium-sized, lightly myelinated Aδ nociceptive Pharmaceuticals 2018, 11, 100 2 of 20 neurons; and (4) small-diameter, unmyelinated C nociceptive neurons that detect noxious stimuli [19]. LaMotte et al. showed that itch-initiating neurons are predominantly C-type myelinatedneurons Awithδ nociceptive an additional neurons; small and population (4) small-diameter, of Aδ neurons unmyelinated [20]. Thus, C both nociceptive pain and neurons itch are that detecttransduced noxious stimuliby small [19-diameter]. LaMotte dorsal et al. root showed ganglion that itch-initiating (DRG) neurons neurons. However, are predominantly the two C-typemodalities neurons are with transduced an additional separately small population by pain-selective of Aδ neurons (nociceptive) [20]. Thus, and both itch pain-selective and itch are(pruriceptive) transduced by neuronal small-diameter subpopulations dorsal root in ganglionthe skin. This (DRG) is firmly neurons. supported However, by thethe twofinding modalities that arethe transduced ablation separatelyof Mas-related by pain-selective G protein-coupled (nociceptive) receptor and itch-selectivemember A3 (pruriceptive)(MrgprA3) neurons neuronal subpopulationssubstantially inreduc the skin.es scratching This is firmly evoked supported by multiple by the findingpruritogens that the and ablation under ofchronic Mas-related itch G protein-coupledconditions, leaving receptor pain member sensitivity A3 (MrgprA3) intact [21]. neurons substantially reduces scratching evoked by multipleIn pruritogens addition to and sensory under neurons, chronic itchmany conditions, other cell leavingtypes are pain also sensitivity involved intactin itch [21 pathways]. [22]In. additionFor instance to sensory, stimulated neurons, keratinocytes many other cellrelease types numerous are also involved inflammatory in itch pathwaysmediators [22 ]. Forincluding instance, thymic stimulated stromal keratinocytes lymphopoietin release (TSLP), numerous ATP, inflammatoryendothelins, prostaglandins, mediators including histamine, thymic stromalnitric lymphopoietin oxide, and serotonin (TSLP), which ATP, endothelins, can directly prostaglandins, activate or sensitize histamine, primary nitric sensory oxide, neurons and serotonin to whichinitiate can directlyitch [22] activate. Similarly, or sensitizeinnate immune primary cells sensory (such neurons as mast tocell initiates, neutrophil itch [22s]., macrophage Similarly, innates, immuneand dendritic cells (such cell ass) mastrelease cells, a versatile neutrophils, ensemble macrophages, of pruritogenic and dendritic inflammatory cells) releasemediators a versatile [23]. ensembleThe interplay of pruritogenic between inflammatory adaptive immune mediators cells and [23]. neurons The interplay also plays between an important adaptive role immune in itch cells andsensation neurons also(Figure plays 1) an[24 important–26]. role in itch sensation (Figure1)[24–26]. FigureFigure 1. Transient1. Transient receptor receptor potential potential (TRP) (TRP channels) channels and itch and signaling. itch signaling. Six TRP Six channelsTRP arechannels implicated are in implicated itch signaling, in itch including signaling, TRPA1, including TRPV1, TRPA1, TRPV3, TRPV4,TRPV1, TRPM8,TRPV3, andTRPV4, TRPC4. All itch-relatedTRPM8, and TRP TRPC4. channels All are expresseditch-related in keratinocytes TRP channels and/or are primary expressed sensory in keratinocytes neurons. TRPA1 is requiredand/or for primary itch evoked sensory by chloroquine neurons. TRPA1 (CQ), bovineis required adrenal for medulla itch evoked 8–22 peptideby chloroquine (BAM8-22), 5-hydroxytryptamine(CQ), bovine adrenal (5-HT), medulla bile acid, 8–22 and peptide thymic (BAM8 stromal-22 lymphopoietin), 5-hydroxytryptamine (TSLP) which (5-HT can), be releasedbile fromacid, keratinocytes and thymic through stromal protease-activated lymphopoietin receptor (TSLP 2) (PAR2)which activation.can be released These pruritogens from bindkeratinocytes to their respective through G protein-coupled protease-activated receptors (GPCRs):receptor Mas-related 2 (PAR2 G) protein-coupledactivation. These receptor member A3 (MrgprA3), MrgprC11, 5-hydroxytryptamine receptor 7(HTR7), G protein-coupled bile pruritogens bind to their respective G protein-coupled receptors (GPCRs): Mas- acid receptor Gpbar1 (TGR5), and thymic stromal lymphopoietin receptor (TSLPR). Phospholipase C related G protein-coupled receptor member A3 (MrgprA3), MrgprC11, 5- (PLC) and Gβγ signaling downstream from these receptors contribute to TRPA1 activation. TRPA1 also hydroxytryptamine receptor 7(HTR7), G protein-coupled bile acid receptor Gpbar1 mediates miR-711-induced itch through direct activation. TRPV1 is required for histamine-evoked (TGR5), and thymic stromal lymphopoietin receptor (TSLPR). Phospholipase C (PLC) itch, whereby histamine receptor 1 (H1R) and histamine receptor 4 (H4R) activate TRPV1 through theand PLC Gβγ signaling signaling
Load more

Recommended publications
  • A Novel Resolvin-Based Strategy for Limiting Acetaminophen Hepatotoxicity
    A Novel Resolvin-Based Strategy for Limiting Acetaminophen Hepatotoxicity The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Patel, Suraj J, Jay Luther, Stefan Bohr, Arvin Iracheta-Vellve, Matthew Li, Kevin R King, Raymond T Chung, and Martin L Yarmush. 2016. “A Novel Resolvin-Based Strategy for Limiting Acetaminophen Hepatotoxicity.” Clinical and Translational Gastroenterology 7 (3): e153. doi:10.1038/ctg.2016.13. http://dx.doi.org/10.1038/ctg.2016.13. Published Version doi:10.1038/ctg.2016.13 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860020 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 Citation: Clinical and Translational Gastroenterology (2016) 7, e153; doi:10.1038/ctg.2016.13 & 2016 the American College of Gastroenterology All rights reserved 2155-384X/16 www.nature.com/ctg A Novel Resolvin-Based Strategy for Limiting Acetaminophen Hepatotoxicity Suraj J. Patel, MD, PhD1,2,5, Jay Luther, MD3,5, Stefan Bohr, MD1, Arvin Iracheta-Vellve, BS1, Matthew Li, PhD1, Kevin R. King, MD, PhD1, Raymond T. Chung, MD3 and Martin L. Yarmush, MD, PhD1,2,4 OBJECTIVES: Acetaminophen (APAP)-induced hepatotoxicity is a major cause of morbidity and mortality. The current pharmacologic treatment for APAP hepatotoxicity, N-acetyl cysteine (NAC), targets the initial metabolite-driven injury but does not directly affect the host inflammatory response.
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION 17(R)-Resolvin D1 Item No. 13060 CAS Registry No.: 528583-91-7 Formal Name: 7S,8R,17R-trihydroxy- 4Z,9E,11E,13Z,15E19Z- HO docosahexaenoic acid Synonyms: Aspirin-triggered Resolvin D1, AT-RvD1, 17-epi-Resolvin D1, 17(R)-RvD1 COOH OH MF: C22H32O5 FW: 376.5 Purity: ≥95% Stability: ≥1 year at -80°C Supplied as: A solution in ethanol OH Special Conditions: Light Sensitive UV/Vis.: λmax: 302 nm Laboratory Procedures For long term storage, we suggest that 17(R)-resolvin D1 (17(R)-RvD1) be stored as supplied at -80°C. It should be stable for at least one year. 17(R)-RvD1 is supplied as a solution in ethanol. To change the solvent, simply evaporate the ethanol under a gentle stream of nitrogen and immediately add the solvent of choice. It is recommended that this product be stored and handled in an ethanol solution. Resolvins can isomerize and degrade when put into freeze thaw conditions and/or in solvents such as DMF or DMSO. Further dilutions of the stock solution into aqueous buffers or isotonic saline should be made prior to performing biological experiments. Ensure that the residual amount of organic solvent is insignificant, since organic solvents may have physiological effects at low concentrations. If an organic solvent-free solution of 17(R)-RvD1 is needed, it can be prepared by evaporating the ethanol and directly dissolving the neat oil in aqueous buffers. The solubility of 17(R)-RvD1 in PBS, pH 7.2, is approximately 0.05 mg/ml. Aqueous solutions of 17(R)-RvD1 should be discarded immediately after use.
    [Show full text]
  • Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators On
    antioxidants Review Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation 1, 1,2, 2, Gyeoung Jin Kang y, Eun Ji Kim y and Chang Hoon Lee * 1 Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; [email protected] (G.J.K.); [email protected] (E.J.K.) 2 College of Pharmacy, Dongguk University, Seoul 04620, Korea * Correspondence: [email protected]; Tel.: +82-31-961-5213 Equally contributed. y Received: 11 November 2020; Accepted: 9 December 2020; Published: 10 December 2020 Abstract: Heart disease is the number one mortality disease in the world. In particular, cardiac fibrosis is considered as a major factor causing myocardial infarction and heart failure. In particular, oxidative stress is a major cause of heart fibrosis. In order to control such oxidative stress, the importance of nuclear factor erythropoietin 2 related factor 2 (NRF2) has recently been highlighted. In this review, we will discuss the activation of NRF2 by docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA. Additionally, we will discuss their effects on cardiac fibrosis via NRF2 activation. Keywords: cardiac fibrosis; NRF2; lipoxins; resolvins; maresins; neuroprotectins 1. Introduction Cardiovascular disease is the leading cause of death worldwide [1]. Cardiac fibrosis is a major factor leading to the progression of myocardial infarction and heart failure [2]. Cardiac fibrosis is characterized by the net accumulation of extracellular matrix proteins in the cardiac stroma and ultimately impairs cardiac function [3]. Therefore, interest in substances with cardioprotective activity continues.
    [Show full text]
  • Novel Resolvin D2 Receptor Axis in Infectious Inflammation Nan Chiang, Xavier De La Rosa, Stephania Libreros and Charles N
    Novel Resolvin D2 Receptor Axis in Infectious Inflammation Nan Chiang, Xavier de la Rosa, Stephania Libreros and Charles N. Serhan This information is current as of September 25, 2021. J Immunol 2017; 198:842-851; Prepublished online 19 December 2016; doi: 10.4049/jimmunol.1601650 http://www.jimmunol.org/content/198/2/842 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2016/12/16/jimmunol.160165 Material 0.DCSupplemental References This article cites 51 articles, 19 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/198/2/842.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 25, 2021 • Fast Publication! 4 weeks from acceptance to publication *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 © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Novel Resolvin D2 Receptor Axis in Infectious Inflammation Nan Chiang,1 Xavier de la Rosa,1 Stephania Libreros, and Charles N. Serhan Resolution of acute inflammation is an active process governed by specialized proresolving mediators, including resolvin (Rv)D2, that activates a cell surface G protein–coupled receptor, GPR18/DRV2.
    [Show full text]
  • Association of the Resolvin Precursor 17-HDHA, but Not D- Or E
    www.nature.com/scientificreports OPEN Association of the resolvin precursor 17-HDHA, but not D- or E- series resolvins, with heat pain Received: 10 March 2017 Accepted: 24 July 2017 sensitivity and osteoarthritis pain in Published: xx xx xxxx humans Ana M. Valdes1,2,3, Srinivasarao Ravipati4,6, Cristina Menni1, Abhishek Abhishek2, Sarah Metrustry1, Juliette Harris1, Ayrun Nessa1, Frances M. K. Williams1, Tim D. Spector1, Michael Doherty2, Victoria Chapman3,5,6 & David A. Barrett 4 Resolvins are omega-3 fatty acid derived potent bioactive lipids that resolve inflammation and modulate transient receptor potential channels. Exogenous administration of the resolvin precursor 17-HDHA shows a strong analgesic effect in animal models of osteoarthritis and acute inflammatory pain, but has not been studied in humans. Our aim was to assess the role of 17-HDHA and resolvins in heat pain sensitivity and in osteoarthritis pain in humans. Resolvins D1, D2, D3, D5, E1 and 17-HDHA, were measured by liquid chromatography-mass spectrometry and tested for association with heat pain thresholds in 250 healthy volunteers who had undergone quantitative sensory testing. Resolvins D1, D2 and 17-HDHA were then tested in 62 individuals affected with knee osteoarthritis and 52 age matched controls and tested for association with knee pain. Circulating levels of docosahexaenoic acid (DHA) were also measured. Levels of 17-HDHA, but not those of the other 5 resolvins tested, were associated with increased heat pain thresholds (beta = 0.075; 95% CI 0.024, 0.126; p < 0.0046). 17-HDHA was associated with lower pain scores in OA patients (beta −0.41; 95% CI-0.69, −0.12; p < 0.005; adjusted for covariates) but not with radiographic osteoarthritis.
    [Show full text]
  • Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Nutrition and Health Sciences -- Faculty Publications Nutrition and Health Sciences, Department of 9-7-2019 Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities Arzu Ulu University of California, Riverside Prakash K. Sahoo University of Nebraska-Lincoln Ana G. Yuil-Valdes University of Nebraska Medical Center, [email protected] Maheswari Mukherjee University of Nebraska Medical Center, [email protected] Matthew Van Ormer University of Nebraska Medical Center, [email protected] Follow this and additional works at: https://digitalcommons.unl.edu/nutritionfacpub See P nextart of page the forHuman additional and Clinical authors Nutrition Commons, Molecular, Genetic, and Biochemical Nutrition Commons, and the Other Nutrition Commons Ulu, Arzu; Sahoo, Prakash K.; Yuil-Valdes, Ana G.; Mukherjee, Maheswari; Ormer, Matthew Van; Muthuraj, Philma Glora; Thompson, Maranda; Berry, Ann Anderson; Hanson, Corrine K.; Natarajan, Sathish Kumar; and Nordgren, Tara M., "Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities" (2019). Nutrition and Health Sciences -- Faculty Publications. 215. https://digitalcommons.unl.edu/nutritionfacpub/215 This Article is brought to you for free and open access by the Nutrition and Health Sciences, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Nutrition and Health Sciences -- Faculty Publications by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Arzu Ulu, Prakash K. Sahoo, Ana G. Yuil-Valdes, Maheswari Mukherjee, Matthew Van Ormer, Philma Glora Muthuraj, Maranda Thompson, Ann Anderson Berry, Corrine K.
    [Show full text]
  • Maresin 1 Promotes Inflammatory Resolution, Neuroprotection and Functional Neurological Recovery After Spinal Cord Injury
    This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. Research Articles: Development/Plasticity/Repair Maresin 1 promotes inflammatory resolution, neuroprotection and functional neurological recovery after spinal cord injury Isaac Francos Quijorna1, Eva Santos-Nogueira1, Karsten Gronert2, Aaron B. Sullivan2, Marcel A Kopp3, Benedikt Brommer3,4, Samuel David5, Jan M. Schwab3,6,7 and Ruben Lopez Vales1 1Departament de Biologia Cel·lular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia Spain 2Vision Science Program, School of Optometry, University of California Berkeley, Berkeley, CA 94598, USA 3Spinal Cord Alliance Berlin (SCAB) and Department of Neurology and Experimental Neurology, Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin, Berlin, Germany 4F.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA 5Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Montreal, Canada 6Department of Neurology, Spinal Cord Injury Division, The Neurological Institute, The Ohio State University, Wexner Medical Centre, Columbus, OH 43210, USA 7Department of Neuroscience and Center for Brain and Spinal Cord Repair, Department of Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Centre, Columbus, OH 43210, USA. DOI: 10.1523/JNEUROSCI.1395-17.2017 Received: 22 May 2017 Revised: 27 September 2017 Accepted: 1 October 2017 Published: 3 November 2017 Author contributions: I.F.Q., J.S., and R.L.-V.
    [Show full text]
  • 15-Epi-Lipoxin A4, Resolvin D2, and Resolvin D3 Induce NF-Κb
    Published March 9, 2018, doi:10.4049/jimmunol.1602090 The Journal of Immunology 15-epi-Lipoxin A4, Resolvin D2, and Resolvin D3 Induce NF-kB Regulators in Bacterial Pneumonia Ho Pan Sham,*,1 Katherine H. Walker,*,1 Raja-Elie E. Abdulnour,* Nandini Krishnamoorthy,* David N. Douda,* Paul C. Norris,† Ioanna Barkas,* Sarah Benito-Figueroa,* Jennifer K. Colby,* Charles N. Serhan,† and Bruce D. Levy* Specialized proresolving mediators (SPMs) decrease NF-kB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-kB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A4 (15-epi-LXA4), resolvin D1, resolvin D2, resolvin D3, and 17-epi-resolvin D1 were produced in vivo in murine lungs. In LPS-activated human bronchial epithelial cells, select SPMs increased expression of the NF-kB regulators A20 and single Ig IL-1R–related molecule (SIGIRR). Of interest, 15-epi-LXA4 induced A20 and SIGIRR in an lipoxin A4 receptor/ formyl peptide receptor 2 (ALX/FPR2) receptor–dependent manner in epithelial cells and in murine pneumonia. This SPM regulated NF-kB–induced cytokines to decrease pathogen-mediated inflammation. In addition to dampening lung inflammation, surprisingly, 15-epi-LXA4 also enhanced pathogen clearance with increased antimicrobial peptide expression. Taken together, to our knowledge these results are the first to identify endogenous agonists for A20 and SIGIRR expression to regulate NF-kB activity and to establish mechanisms for NF-kB regulation by SPMs for pneumonia resolution. The Journal of Immunology, 2018, 200: 000–000. athogen-induced inflammation is a major and untreated to bacteria, including generation of proinflammatory cytokines and source of morbidity and mortality in common infections, antimicrobial peptide production (8, 9).
    [Show full text]
  • Resolvin D1 Limits 5-Lipoxygenase Nuclear Localization and Leukotriene B4 Synthesis by Inhibiting a Calcium- Activated Kinase Pathway
    Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium- activated kinase pathway Gabrielle Fredmana,1, Lale Ozcana, Stefano Spolitua, Jason Hellmannb, Matthew Spiteb, Johannes Backsc, and Ira Tabasa,1 aDepartment of Medicine, Department of Pathology and Cell Biology, and Department of Physiology, Columbia University, New York, NY 10032; bInstitute of Molecular Cardiology, University of Louisville, Louisville, KY 40202; and cLaboratory for Cardiac Epigenetics, Department of Cardiology, Heidelberg University, and German Centre for Cardiovascular Research (DZHK), 69120 Heidelberg, Germany Edited by Mauro Perretti, Queen Mary University of London, London, United Kingdom, and accepted by the Editorial Board August 26, 2014 (received for review June 13, 2014) Imbalances between proinflammatory and proresolving mediators critical because although LTB4 is crucial for host defense, exu- can lead to chronic inflammatory diseases. The balance of arach- berant production underlies the basis for several inflammatory idonic acid-derived mediators in leukocytes is thought to be achieved diseases and impairs endogenous resolution programs (11, 18). through intracellular localization of 5-lipoxygenase (5-LOX): nuclear Moreover, complete blockade of LTB4 biosynthetic enzymes may 5-LOX favors the biosynthesis of proinflammatory leukotriene B4 compromise host defense; thus, understanding new mechanisms (LTB4), whereas, in theory, cytoplasmic 5-LOX could favor the bio- that temper LTB4 production is essential for translational research synthesis of proresolving lipoxin A4 (LXA4). This balance is shifted in this area (19). in favor of LXA4 by resolvin D1 (RvD1), a specialized proresolving Here, we report that RvD1, by suppressing the activation of the mediator derived from docosahexaenoic acid, but the mechanism is calcium-sensing kinase calcium-calmodulin-dependent protein ki- not known.
    [Show full text]
  • The Inflammatory Role of Pro-Resolving Mediators In
    International Journal of Molecular Sciences Review The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review Cássia de Fáveri 1, Paula M. Poeta Fermino 2 , Anna P. Piovezan 3 and Lia K. Volpato 3,4,* 1 Medical Residency Program in Ginecology and Obstetric, Hospital Regional Dr. Homero Miranda Gomes, São José 88103-901, Brazil; [email protected] 2 Department Curso de Medicina, Campus Pedra Branca, Undergraduate Medical School, Universidade Sul de Santa Catarina—UNISUL, Palhoça 88137-272, Brazil; [email protected] 3 Postgraduate Studies in Health Science Program, Universidade do Sul de Santa Catarina—UNISUL, Palhoça 88137-272, Brazil; [email protected] 4 Ginecology and Obstetric Department, Hospital Regional Dr. Homero Miranda Gomes, São José 88103-901, Brazil * Correspondence: [email protected] Abstract: The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and Citation: de Fáveri, C.; Fermino, angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling P.M.P.; Piovezan, A.P.; Volpato, L.K. induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 The Inflammatory Role of demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors.
    [Show full text]
  • Polyunsaturated Fatty Acid Metabolites
    Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction Lucie Paloque, Teresa Pérez-Berezo, Anne Abot, Jessica Dalloux-Chioccioli, Sandra Bourgeade-Delmas, Pauline Le Faouder, Julien Pujo, Marie-Ange Teste, Jean-Marie François, Nils Helge Schebb, et al. To cite this version: Lucie Paloque, Teresa Pérez-Berezo, Anne Abot, Jessica Dalloux-Chioccioli, Sandra Bourgeade- Delmas, et al.. Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in par- asite/host interaction. Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2019, 60 (3), pp.636-647. 10.1194/jlr.M091736. hal-02140502 HAL Id: hal-02140502 https://hal.archives-ouvertes.fr/hal-02140502 Submitted on 26 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Copyright Supplemental Material can be found at: http://www.jlr.org/content/suppl/2019/01/09/jlr.M091736.DC1 .html Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction Lucie Paloque,1,*,†
    [Show full text]
  • Specialized Pro-Resolving Mediators
    Specialized Pro-Resolving Mediators Specialized pro-resolving mediators (SPMs) are an important group of signaling molecules derived from arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid that are liberated during the inflammatory process. Studies have shown that resolvins, lipoxins, maresins, and protectins evoke responses that help to resolve an inflammatory episode. Cayman has synthesized an array of these key lipid mediators to aid in a better understanding of this process. Skin SPMs RESOLVE INFLAMMATORY Post injury RESPONSE AFTER INJURY/INFECTION + Lipoxins + Protectins Cytokines SPMs + Maresins + E-, D-, and T-Series Resolvins Chemokines Lipids Request the SPM Pathway Wall Poster at Blood vessel www.caymanchem.com/Literature SPM Precursors Item No. Product Name Description 90010 Arachidonic Acid A precursor for prostaglandins, thromboxanes, leukotrienes, and lipoxins 90310 Docosahexaenoic Acid A precursor for D-series resolvins, maresins, and protectins 90165 Docosapentaenoic Acid A precursor for T-series resolvins 90110 Eicosapentaenoic Acid A precursor for E-series resolvins Metabolites, methyl ester, and deuterated forms are available online Pro-Resolving Compounds Resolvins Lipoxins, Maresins, and Protectins Item No. Product Name Item No. Product Name 10012554 Resolvin D1 90410 Lipoxin A4 13060 17(R)-Resolvin D1 10007737 Lipoxin A4-d5 10007279 Resolvin D2 90420 Lipoxin B4 11184 Resolvin D2-d5 10878 Maresin 1 13834 Resolvin D3 16369 Maresin 2 19512 Resolvin D3-d5 17007 MCTR1 13835 Resolvin D4 17008 MCTR2 9002881 17(R)-Resolvin D4 19067 MCTR3 10007280 Resolvin D5 19064 PCTR1 10007848 Resolvin E1 19065 PCTR2 10009854 Resolvin E1-d4 19066 PCTR3 Common SPMs listed, more compounds including methyl ester and deuterated forms available online 2018 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM 100 100 Quantify Resolvin D1 Evaluate data cautiously 80 80 Use data with confidence Resolvin D1 ELISA Kit - Item No.
    [Show full text]