DOCSLIB.ORG

Stimulating Prostaglandin Production Alter Resolution of Inflammation In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Stimulating Prostaglandin Production Alter Resolution of Inflammation In Increased Saturated Fatty Acids in Obesity Alter Resolution of Inflammation in Part by Stimulating Prostaglandin Production This information is current as Jason Hellmann, Michael J. Zhang, Yunan Tang, Madhavi of October 2, 2021. Rane, Aruni Bhatnagar and Matthew Spite J Immunol published online 19 June 2013 http://www.jimmunol.org/content/early/2013/06/17/jimmun ol.1203369 Downloaded from Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision http://www.jimmunol.org/ • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: by guest on October 2, 2021 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 © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published June 19, 2013, doi:10.4049/jimmunol.1203369 The Journal of Immunology Increased Saturated Fatty Acids in Obesity Alter Resolution of Inflammation in Part by Stimulating Prostaglandin Production Jason Hellmann,* Michael J. Zhang,* Yunan Tang,* Madhavi Rane,† Aruni Bhatnagar,*,‡ and Matthew Spite*,‡,x Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation, and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain unresolved inflammation during obesity remain unclear. In this study, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry–based lipidomics Downloaded from approach, we found that in db/db mice, PGE2/D2 levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated cyclooxygenase-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclo- oxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with wild-type mice. Therapeutic administration of EP2/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db/db mice, as well as the accumulation of apoptotic cells in the thymus. Taken together, these studies provide new insights into http://www.jimmunol.org/ the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals. The Journal of Immunology, 2013, 191: 000–000. besity has emerged as one of the most important public metabolic dysregulation in obesity is intimately linked with the health concerns of our time. It is a leading risk factor for development of chronic inflammation, which in turn contributes to O the development of type 2 diabetes (T2D), and nearly alterations in metabolism in a vicious positive feed-forward cycle (8). Thus, understanding how nutrient excess impacts immune re- 90% of adults with T2D are obese (1). Obesity is also a risk factor by guest on October 2, 2021 for cardiovascular disease and liver disease, due largely to meta- sponses is required to identify novel strategies for treatment and bolic disturbances, such as insulin resistance and dyslipidemia (2, management of obesity and its secondary complications. 3). Obesity is associated with chronic elevation of free fatty acids Effector cells of the innate immune system, including polymor- (FFAs), which promote insulin resistance and contribute to the phonuclear neutrophils (PMNs) and macrophages, play key roles in development of systemic hyperglycemia (4, 5). High plasma levels mediating immune responses. These leukocytes also sense nutrient of FFAs are also independently associated with hypertension and imbalances. Saturated fatty acids, which are elevated in obesity and sudden cardiac death (6, 7). Accumulating evidence indicates that diabetes (5), initiate inflammatory responses in part via signaling through pattern recognition receptors, that is, TLR2, TLR4, and nucleotide-binding oligomerization domain–like receptors (9–12). *Diabetes and Obesity Center, University of Louisville School of Medicine, Louis- Other endogenous mediators of metabolism, such as insulin, leptin, ville, KY 40202; †Division of Nephrology, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202; ‡Division of Cardiovascular and adiponectin, also regulate leukocyte effector functions, sug- Medicine, Department of Medicine, Institute of Molecular Cardiology, University of x gesting that the immune system is exquisitely sensitive to the nu- Louisville School of Medicine, Louisville, KY 40202; and Department of Microbi- trient tone (13, 14). Several studies have shown that low-grade ology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202 inflammation associated with obesity promotes the development of Received for publication December 10, 2012. Accepted for publication May 24, chronic diseases such as atherosclerosis, cancer, and nonalcoholic 2013. fatty liver disease and impairs host defense and wound healing (15– This work was supported by National Institutes of Health Grants HL106173 (to M.S.) 17). Nevertheless, the mechanisms by which metabolic imbalance and RR024489 (to A.B. and M.S.). J.H. is the recipient of a National Research affects inflammatory processes remain unclear. The initiation and Service Award from the National Institutes of Health (Grant HL116186). the resolution of inflammatory responses involve different cellular Address correspondence and reprint requests to Dr. Matthew Spite, University of Louisville School of Medicine, 580 South Preston Street, Delia Baxter Building, responses that are temporally controlled, in part, by specific lipid Room 404F, Louisville, KY 40202. E-mail address: [email protected] mediators (18–21). Upon trafficking to sites of tissue infection and Abbreviations used in this article: ALOX5, arachidonate 5-lipoxygenase; ALOX15, injury, PMNs encounter and attempt to eradicate invading patho- arachidonate 15-lipoxygenase; ASA, acetylsalicylic acid; COX, cyclooxygenase; gens. Subsequently, they undergo rapid apoptosis and must be ef- DPBS, Dulbecco’s PBS; FFA, free fatty acid; HETE, hydroxyeicosatetraenoic acid; HF, high fat; hPGDS, hematopoietic PGD synthase; LC-MS/MS, liquid chromatog- fectively cleared by macrophages to prevent inadvertent tissue raphy–tandem mass spectrometry; LTB4, leukotriene B4; mPGES, microsomal PGE injury (21, 22). As such, defects in macrophage phagocytosis can synthase; PA, palmitic acid; PKA, protein kinase A; PMN, polymorphonuclear neu- give rise to altered clearance of apoptotic cells (23, 24). Our recent trophil; PTGS, PG endoperoxide synthase; T2D, type 2 diabetes; WT, wild-type. studies have shown that in db/db mice, which are a model of human Copyright Ó 2013 by The American Association of Immunologists, Inc. 0022-1767/13/$16.00 obesity and T2D, defective macrophage-dependent clearance of www.jimmunol.org/cgi/doi/10.4049/jimmunol.1203369 2 PGs AND ALTERED INFLAMMATION IN OBESITY apoptotic cells delays the resolution of acute peritonitis (15). allowed to adhere for 1 h. Macrophages were then washed to remove any Moreover, we found that restoring defective macrophage phago- nonadherent cells and were incubated with IgG-opsonized FITC-labeled cytosis with proresolving lipid mediators, such as resolvin D1, en- zymosan A (Invitrogen) for 60 min at 37˚C in fresh DMEM containing 10% FBS. Trypan blue was used to quench extracellular fluorescence for 1 hances diabetic wound healing, suggesting that defects in min, followed by a DPBS+/+ (pH 7.45) wash. Phagocytosis was quantified phagocytosis are causally related to clinically relevant complica- using a spectrophotometer (PerkinElmer). To determine how saturated FFAs tions of diabetes and obesity (15). Nonetheless, the mechanisms impact macrophage phagocytosis, BSA conjugates of PA were prepared to underlying altered resolution of inflammation and phagocyte func- increase the solubility of the FFAs. For this, BSA and sodium palmitate were first dissolved in 150 mM NaCl. Sodium palmitate (1 mM) was then tion in conditions of nutrient excess remain incompletely under- slowly introduced into the BSA (0.17 mM) solution at 37˚C and allowed to stood. In this study, we show that resolution of acute peritonitis in incubate for 1 h, and the pH was adjusted to 7.4. To examine the effects of obesity is delayed in part because elevated FFAs prolong PMN FFAs on macrophages, RAW 264.7 macrophages (American Type Culture survival and inhibit macrophage phagocytosis.
Load more

Recommended publications
  • Eicosanoids in Carcinogenesis
    4open 2019, 2,9 © B.L.D.M. Brücher and I.S. Jamall, Published by EDP Sciences 2019 https://doi.org/10.1051/fopen/2018008 Special issue: Disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer” Available online at: Guest Editor: Obul R. Bandapalli www.4open-sciences.org REVIEW ARTICLE Eicosanoids in carcinogenesis Björn L.D.M. Brücher1,2,3,*, Ijaz S. Jamall1,2,4 1 Theodor-Billroth-Academy®, Germany, USA 2 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Germany, USA 3 Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany 4 Risk-Based Decisions Inc., Sacramento, CA, USA Received 21 March 2018, Accepted 16 December 2018 Abstract- - Inflammation is the body’s reaction to pathogenic (biological or chemical) stimuli and covers a burgeoning list of compounds and pathways that act in concert to maintain the health of the organism. Eicosanoids and related fatty acid derivatives can be formed from arachidonic acid and other polyenoic fatty acids via the cyclooxygenase and lipoxygenase pathways generating a variety of pro- and anti-inflammatory mediators, such as prostaglandins, leukotrienes, lipoxins, resolvins and others. The cytochrome P450 pathway leads to the formation of hydroxy fatty acids, such as 20-hydroxyeicosatetraenoic acid, and epoxy eicosanoids. Free radical reactions induced by reactive oxygen and/or nitrogen free radical species lead to oxygenated lipids such as isoprostanes or isolevuglandins which also exhibit pro-inflammatory activities. Eicosanoids and their metabolites play fundamental endocrine, autocrine and paracrine roles in both physiological and pathological signaling in various diseases. These molecules induce various unsaturated fatty acid dependent signaling pathways that influence crosstalk, alter cell–cell interactions, and result in a wide spectrum of cellular dysfunctions including those of the tissue microenvironment.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,872,152 B2 Serhan Et Al
    US007872152B2 (12) United States Patent (10) Patent No.: US 7,872,152 B2 Serhan et al. (45) Date of Patent: Jan. 18, 2011 (54) USE OF DOCOSATRIENES, RESOLVINS AND (58) Field of Classification Search ....................... None THER STABLE ANALOGS IN THE See application file for complete search history. TREATMENT OF AIRWAY DISEASES AND (56) References Cited ASTHMA U.S. PATENT DOCUMENTS (75) Inventors: Charles N. Serhan, Needham, MA (US); Bruce D. Levy, West Roxbury, 4,201,211 A 5/1980 Chandrasekaran et al. MA (US) (Continued) (73) Assignee: The Brigham and Women's Hospital, FOREIGN PATENT DOCUMENTS Inc., Boston, MA (US) EP O736509 A2 10, 1996 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (Continued) U.S.C. 154(b) by 198 days. OTHER PUBLICATIONS (21) Appl. No.: 11/836,460 Hong et al., Journal of Biological Chemistry 278(17) 14677-14687.* (22) Filed: Aug. 9, 2007 (Continued) Primary Examiner Karl J. Puttlitz (65) Prior Publication Data (74) Attorney, Agent, or Firm—Colin L. Fairman; Scott D. US 2008/OO96961 A1 Apr. 24, 2008 Rothenberge; Fulbright & Jaworski Related U.S. Application Data (57) ABSTRACT (63) Continuation of application No. 11/081,203, filed on The present invention is generally drawn to novel isolated Mar. 16, 2005, and a continuation-in-part of applica therapeutic agents, termed resolving, generated from the tion No. 10/639,714, filed on Aug. 12, 2003, now Pat. interaction between a dietary omega-3 polyunsaturated fatty No. 7,585,856. acid (PUFA) such as eicosapentaenoic acid (EPA) or docosa (60) Provisional application No.
    [Show full text]
  • Role of 17-HDHA in Obesity-Driven Inflammation Angelika
    Diabetes Page 2 of 38 Impaired local production of pro-resolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation Running title: Role of 17-HDHA in obesity-driven inflammation Angelika Neuhofer1,2, Maximilian Zeyda1,2, Daniel Mascher3, Bianca K. Itariu1,2, Incoronata Murano4, Lukas Leitner1,2, Eva E. Hochbrugger1,2, Peter Fraisl1,4, Saverio Cinti5,6, Charles N. Serhan7, Thomas M. Stulnig1,2 1Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria, 2Christian Doppler-Laboratory for Cardio-Metabolic Immunotherapy, Medical University of Vienna, Vienna, Austria, 3pharm-analyt Labor GmbH, Baden, Austria, 4Flander Institute for Biotechnology and Katholieke Universiteit Leuven, Belgium, 5Department of Molecular Pathology and Innovative Therapies, University of Ancona (Politecnicadelle Marche), Ancona, Italy, 6The Adipose Organ Lab, IRCCS San Raffele Pisana, Rome, 00163, Italy, 7Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 Corresponding author: Thomas M. Stulnig, Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; phone +43 1 40400 61027; fax +43 1 40400 7790; e-mail: [email protected] Word count: 4394 Number of tables and figures: 7 figures and online supplemental material (1 supplemental figure and 2 supplemental tables) 1 Diabetes Publish Ahead of Print, published online January 24, 2013 Page 3 of 38 Diabetes ABSTRACT Obesity-induced chronic low-grade inflammation originates from adipose tissue and is crucial for obesity-driven metabolic deterioration including insulin resistance and type 2 diabetes.
    [Show full text]
  • Metabolites OH
    H OH metabolites OH Article 16HBE Cell Lipid Mediator Responses to Mono and Co-Infections with Respiratory Pathogens Daniel Schultz 1, Surabhi Surabhi 2 , Nicolas Stelling 2, Michael Rothe 3, KoInfekt Study 1 2 2, 1, Group y, Karen Methling , Sven Hammerschmidt , Nikolai Siemens * and Michael Lalk * 1 Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany; [email protected] (D.S.); [email protected] (K.M.) 2 Department of Molecular Genetics and Infection Biology, University of Greifswald, 17487 Greifswald, Germany; [email protected] (S.S.); [email protected] (N.S.); [email protected] (S.H.) 3 Lipidomix, 13125 Berlin, Germany; [email protected] * Correspondence: [email protected] (N.S.); [email protected] (M.L.); Tel.: +49-3834-420-5711 (N.S.); +49-3834-420-4867 (M.L.) The members of the KoInfekt Study Group are listed in AppendixA. y Received: 26 January 2020; Accepted: 13 March 2020; Published: 18 March 2020 Abstract: Respiratory tract infections are a global health problem. The main causative agents of these infections are influenza A virus (IAV), Staphylococcus aureus (S. aureus), and Streptococcus pneumoniae (S. pneumoniae). Major research focuses on genetics and immune responses in these infections. Eicosanoids and other oxylipins are host-derived lipid mediators that play an important role in the activation and resolution of inflammation. In this study, we assess, for the first time, the different intracellular profiles of these bioactive lipid mediators during S. aureus LUG2012, S. pneumoniae TIGR4, IAV, and corresponding viral and bacterial co-infections of 16HBE cells.
    [Show full text]
  • An Imbalance Between Specialized Pro-Resolving Lipid Mediators and Pro-Inflammatory Leukotrienes Promotes Instability of Atherosclerotic Plaques
    ARTICLE Received 5 Feb 2016 | Accepted 10 Aug 2016 | Published 23 Sep 2016 DOI: 10.1038/ncomms12859 OPEN An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques Gabrielle Fredman1,2,*, Jason Hellmann3,*, Jonathan D. Proto1, George Kuriakose1, Romain A. Colas3, Bernhard Dorweiler4, E. Sander Connolly5, Robert Solomon5, David M. Jones6, Eric J. Heyer7, Matthew Spite3 & Ira Tabas1 Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr À/ À mice. Adminis- tration of RvD1 to these mice during plaque progression restores the RvD1:LTB4 ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability. 1 Department of Anesthesiology, Perioperative and Pain Medicine, Departments of Medicine, Pathology & Cell Biology, and Physiology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA. 2 The Department of Molecular and Cellular Physiology, Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
    [Show full text]
  • Eosinophil-Mediated Signalling Attenuates Inflammatory Responses
    Gut Online First, published on September 10, 2014 as 10.1136/gutjnl-2014-306998 Inflammatory bowel disease ORIGINAL ARTICLE Gut: first published as 10.1136/gutjnl-2014-306998 on 10 September 2014. Downloaded from Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis Joanne C Masterson,1,2,3 Eóin N McNamee,2,3,4 Sophie A Fillon,1,2,3 Lindsay Hosford,1,2,3 Rachel Harris,1,2,3 Shahan D Fernando,1,2,3 Paul Jedlicka,3,5 Ryo Iwamoto,6 Elizabeth Jacobsen,7,8 Cheryl Protheroe,7,8 Holger K Eltzschig,2,3,4 Sean P Colgan,2,3,9 Makoto Arita,6,7 James J Lee,8 Glenn T Furuta1,2,3 ▸ Additional material is ABSTRACT published online only. To view Objective Eosinophils reside in the colonic mucosa Significance of this study please visit the journal online fi (http://dx.doi.org/10.1136/ and increase signi cantly during disease. Although a gutjnl-2014-306998). number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the For numbered affiliations see What is already known on this subject? end of article. expanding scope of eosinophil-mediated activities ▸ IBD is a disease characterised by increased indicate that they also regulate local immune responses numbers of eosinophils. Correspondence to and modulate tissue inflammation. We sought to define ▸ The exact role of eosinophils during the onset Dr Glenn T Furuta, Section of the impact of eosinophils that respond to acute phases of inflammation and in chronic disease remains Pediatric Gastroenterology, Hepatology and Nutrition, of colitis in mice.
    [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]
  • Synthetic Studies Towards Analogs of Protectin D1
    Synthetic Studies Towards Analogs Of Protectin D1 Thesis for the degree Master of Pharmacy Mai El-khatib School of Pharmacy Faculty of Mathematics and Natural Sciences UNIVERSITY OF OSLO 2016 Synthetic Studies Towards Analogs Of Protectin D1 Thesis for the degree Master of Pharmacy Mai El-khatib School of Pharmacy Faculty of Mathematics and Natural Sciences UNIVERSITY OF OSLO 2016 © Mai El-khatib, 2016 SYNTHETIC STUDIES TOWARDS ANALOGS OF PROTECTIN D1 Mai El-khatib http://www.duo.uio.no Printed in Norway: Reprosentralen, Universitetet i Oslo II ”The secret of life, though, is to fall seven times and to get up eight times.” - Paulo Coelho III IV Acknowledgements The work presented in this master’s thesis has been undertaken between June 2015 and June 2016 at the school of pharmacy, department of pharmaceutical chemistry, University of Oslo. First of all, I would like to thank my supervisor Professor Trond Vidar Hansen for his continuous support and motivation throughout the whole year. I am grateful for the inspiring conversations and the suggestions we both exchanged. Your brilliance and love for chemistry has been a great source of motivation. My sincere gratitude also goes to Associate Professor Anders Vik who has also been motivating me and providing me with insightful comments and encouragement. Without his support I would not be able to conduct this research. I also wish to acknowledge both Dr. Jørn Tungen and Dr. Marius Aursnes who have managed to make me the lab-nerd I am today and also for sharing their expertise. It was a pleasure working and laughing with you.
    [Show full text]
  • Are Specialized Pro-Resolving Mediators Promising Therapeutic Agents for Severe Bronchial Asthma?
    4269 Editorial Are specialized pro-resolving mediators promising therapeutic agents for severe bronchial asthma? Takeshi Hisada, Haruka Aoki-Saito, Yasuhiko Koga Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan Correspondence to: Takeshi Hisada, MD, PhD. Department of Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan. Email: [email protected]. Submitted Sep 23, 2017. Accepted for publication Oct 10, 2017. doi: 10.21037/jtd.2017.10.116 View this article at: http://dx.doi.org/10.21037/jtd.2017.10.116 In Japan, although the number of patients with asthma has pro-resolving mediators that includes the resolvin (E-series, increased, the number of patients who die from asthma has D-series, and DPA-derived), protectin, and maresin decreased (1.2 per 100,000 patients in 2015) (1). Currently, families, as well as arachidonic-acid-derived lipoxins (5). although the majority of asthma patients can be effectively Resolvin E1 (RvE1) is an anti-inflammatory lipid mediator treated with available medications, such as inhaled derived from the omega-3 fatty acid, eicosapentaenoic corticosteroids (ICS) or ICS/long-acting β2 agonists (ICS/ acid (EPA), and has been recently shown to be involved in LABA), options remain to be established for difficult-to- resolving inflammation (6). Although little is known about treat asthma (severe asthma), which can be considered an the actions of RvE1 in the resolution of asthma-induced unmet need. Patients with severe asthma (presumably less inflammation, recent studies using a mouse model have than 10% of all asthma cases) who experience exacerbations shown the potential of RvE1 in treating asthma (7-9).
    [Show full text]
  • Acid-Derived Protectin D1 Renoprotective Docosahexaenoic
    Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of This information is current as Renoprotective Docosahexaenoic of September 30, 2021. Acid-Derived Protectin D1 Iram R. Hassan and Karsten Gronert J Immunol 2009; 182:3223-3232; ; Downloaded from doi: 10.4049/jimmunol.0802064 http://www.jimmunol.org/content/182/5/3223 References This article cites 65 articles, 23 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/182/5/3223.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 30, 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 © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Acute Changes in Dietary ␻-3 and ␻-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D11 Iram R.
    [Show full text]
  • Organic & Biomolecular Chemistry
    Volume 12 Number 3 21 January 2014 Pages 385–542 Organic & Biomolecular Chemistry www.rsc.org/obc ISSN 1477-0520 PAPER T. V. Hansen et al. Stereoselective synthesis of protectin D1: a potent anti-infl ammatory and proresolving lipid mediator Organic & Biomolecular Chemistry View Article Online PAPER View Journal | View Issue Stereoselective synthesis of protectin D1: a potent anti-inflammatory and proresolving lipid mediator† Cite this: Org. Biomol. Chem., 2014, 12, 432 M. Aursnes,a J. E. Tungen,a A. Vik,a J. Dallib and T. V. Hansen*a A convergent stereoselective synthesis of the potent anti-inflammatory, proresolving and neuroprotective lipid mediator protectin D1 (2) has been achieved in 15% yield over eight steps. The key features were a Received 19th September 2013, stereocontrolled Evans-aldol reaction with Nagao’s chiral auxiliary and a highly selective Lindlar reduction Accepted 31st October 2013 of internal alkyne 23, allowing the sensitive conjugated E,E,Z-triene to be introduced late in the prepa- DOI: 10.1039/c3ob41902a ration of 2. The UV and LC/MS–MS data of synthetic protectin D1 (2) matched those obtained from www.rsc.org/obc endogenously produced material. Introduction Creative Commons Attribution 3.0 Unported Licence. Polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (1, DHA), play a major role in the physiology of living organisms.1 Recent efforts by the Serhan research group have established that DHA (1) is a substrate for the biosynthesis of several potent anti-inflammatory proresolving mediators, such as protectin D1 (2),2 maresin 1,3 resolvin D1 and resolvin D3.2a,4 All of these compounds have enabled new research areas related to many disease states associated with inflam- This article is licensed under a mation.5 It was reported that protectin D1 (2) is biosynthesized from DHA (1) via a lipoxygenase-mediated pathway that con- verts 1 by 15-lipoxygenase (15-LO) to the 17S-hydroperoxide 3 Open Access Article.
    [Show full text]
  • Resolvin D1 (Rvd1) and Maresin 1 (Mar1) Contribute to Human Macrophage Control of M
    International Immunopharmacology 74 (2019) 105694 Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp Resolvin D1 (RvD1) and maresin 1 (Mar1) contribute to human macrophage control of M. tuberculosis infection while resolving inflammation T ⁎ Andy Ruiza,b, Carmen Sarabiaa, Martha Torresa, Esmeralda Juáreza, a Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, CDMX 14080, Mexico b Posgrado en Ciencias Biológicas, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX 04510, Mexico ARTICLE INFO ABSTRACT Keywords: Resolvins and protectins counter inflammation, enhance phagocytosis, induce bactericidal/permeability-in- Resolution of inflammation creasing protein (BPI) expression, and restore inflamed tissue to homeostasis. Because modulating the in- Resolvin D1 flammation/antiinflammation balance is important in Mycobacterium tuberculosis infection, we evaluated the Maresin 1 effects of resolvins and protectins on human macrophages infected in vitro. Monocyte-derived macrophages were Tuberculosis infected with M. tuberculosis H37Rv at a multiplicity of infection (MOI) of 5 and treated 1 h post-infection in vitro Macrophages with 100 nM LXA4, RvD1, RvD2, PD1 or 150 nM Mar1. After 24 h, cytokine production was measured by Luminex, and BPI and cathelicidin LL37 expression was determined by real-time PCR. Macrophage bactericidal activity was assessed by colony-forming units (CFUs) 3 days posttreatment. Nuclear translocation of Nrf2 was assessed by ELISA, NFκB translocation was determined by imaging cytometry, and BPI production was de- termined by fluorescence microscopy. We found that all lipids reduced LPS-dependent and M. tuberculosis-in- duced TNF-α production. RvD1 and Mar1 also induced a significant reduction in M.
    [Show full text]