11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Resolution of Cochlear Inflammation: Novel Target for Preventing or Ameliorating Drug-, Noise- and Age-related Hearing Loss

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A significant number of studies support the idea that inflammatory responses are intimately associated with drug-, noise- and age-related hearing loss (DRHL, NRHL and ARHL). Consequently, several clinical strategies aimed at reducing auditory dysfunction by preventing inflammation are currently under intense scrutiny. Inflammation, however, is a normal adaptive response aimed at restoring tissue functionality and homeostasis after infection, tissue injury and even stress under sterile conditions, and suppressing it could have unintended negative consequences. Therefore, an appropriate approach to prevent or ameliorate DRHL, NRHL and ARHL should involve improving the resolution of the inflammatory process in the cochlea rather than inhibiting this phenomenon. The resolution of inflammation is not a passive response but rather an active, highly controlled and coordinated process. Inflammation by itself produces specialized pro-resolving mediators with critical functions, including essential fatty acid derivatives (lipoxins, resolvins, protectins and maresins), proteins and peptides such as annexin A1 and galectins, purines (adenosine), gaseous mediators (NO, H 2S and CO), as well as neuromodulators like acetylcholine and netrin-1. In this review article, we describe recent advances in the understanding of the resolution phase of inflammation and highlight therapeutic strategies that might be useful in preventing inflammation-induced cochlear damage. In particular, we emphasize beneficial approaches that have been tested in pre-clinical models of inflammatory responses induced by recognized ototoxic drugs such as cisplatin and aminoglycoside antibiotics. Since these studies suggest that improving the resolution process could be useful for the prevention of inflammation-associated diseases in humans, we discuss the potential application of similar strategies to prevent or mitigate DRHL, NRHL and ARHL.

          Related collections

          Most cited references 257

          • Record: found
          • Abstract: found
          • Article: not found

          ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis.

          Reactive oxygen species (ROS) have been shown to be toxic but also function as signalling molecules. This biological paradox underlies mechanisms that are important for the integrity and fitness of living organisms and their ageing. The pathways that regulate ROS homeostasis are crucial for mitigating the toxicity of ROS and provide strong evidence about specificity in ROS signalling. By taking advantage of the chemistry of ROS, highly specific mechanisms have evolved that form the basis of oxidant scavenging and ROS signalling systems.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Anti-inflammatory therapy in chronic disease: challenges and opportunities.

            A number of widespread and devastating chronic diseases, including atherosclerosis, type 2 diabetes, and Alzheimer's disease, have a pathophysiologically important inflammatory component. In these diseases, the precise identity of the inflammatory stimulus is often unknown and, if known, is difficult to remove. Thus, there is interest in therapeutically targeting the inflammatory response. Although there has been success with anti-inflammatory therapy in chronic diseases triggered by primary inflammation dysregulation or autoimmunity, there are considerable limitations. In particular, the inflammatory response is critical for survival. As a result, redundancy, compensatory pathways, and necessity narrow the risk:benefit ratio of anti-inflammatory drugs. However, new advances in understanding inflammatory signaling and its links to resolution pathways, together with new drug development, offer promise in this area of translational biomedical research.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2–Nonsteroidal Antiinflammatory Drugs and Transcellular Processing

              Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with ω-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 ω-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX5 and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue > 5,12,18R-triHEPE > 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as ω-5 and ω-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2–nonsteroidal antiinflammatory drug–dependent oxygenations and cell–cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of ω-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                07 July 2017
                2017
                : 11
                Affiliations
                [1] 1Laboratory of Auditory Cell Biology, Department of Head and Neck Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
                [2] 2Epigenetics and Chromatin Dynamics Laboratory, Translational Epigenomic Program, Center for Individualized Medicine (CIM) Mayo Clinic Rochester, MN, United States
                Author notes

                Edited by: Peter S. Steyger, Oregon Health & Science University, United States

                Reviewed by: Megan Beers Wood, St. Jude Children’s Research Hospital, United States; Meiyan Jiang, Oregon Health & Science University, United States

                *Correspondence: Federico Kalinec fkalinec@ 123456mednet.ucla.edu
                Article
                10.3389/fncel.2017.00192
                5500902
                88f9a916-0c4f-4307-82fb-c37ca009306a
                Copyright © 2017 Kalinec, Lomberk, Urrutia and Kalinec.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 309, Pages: 24, Words: 19278
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: DK52913
                Categories
                Neuroscience
                Review

                Comments

                Comment on this article