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      Measurement of trihydroxy-linoleic acids in stratum corneum by tape-stripping: Possible biomarker of barrier function in atopic dermatitis

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          Abstract

          Epidermal ceramides are indispensable lipids that maintain the functions of the stratum corneum. Esterified omega-hydroxyacyl-sphingosine (EOS) ceramide with a linoleate moiety is one of the most important ceramide species for forming cornified lipid envelopes. This linoleate moiety is eventually metabolized to trihydroxy-linoleic acid (triol, 9,10,13-trihydroxy-11 E-octadecenoic acid). Thus, we assumed that a decrease of triols might reflect skin barrier dysfunction. Against this background, the purposes of this study were to measure the triols by a simple tape-stripping method and to determine the correlation between the amount of triols and transepidermal water loss (TEWL) as an indicator of barrier dysfunction in atopic dermatitis patients. Twenty Japanese subjects with normal skin and 20 atopic dermatitis patients were enrolled in this study. TEWL was measured and triols of the stratum corneum were analyzed by tape-stripping. The results showed for the first time that triols in the stratum corneum could be simply measured using the tape-stripping method. The triol levels in atopic dermatitis patients were much higher than those in healthy subjects. Moreover, the triol levels correlated with TEWL of non-lesional forearm skin in patients with atopic dermatitis. The results suggest that the assaying of triol levels via non-invasive tape-stripping could be beneficial for monitoring barrier function in atopic dermatitis.

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          Most cited references31

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          Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.

          Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
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            Characterization of overall ceramide species in human stratum corneum.

            Ceramides (CERs) in human stratum corneum (SC) play physicochemical roles in determining barrier and water-holding functions of the skin, and specific species might be closely related to the regulation of keratinization, together with other CER-related lipids. Structures of those diverse CER species, however, have not been comprehensively revealed. The aim of this study was to characterize overall CER species in the SC. First, we constructed 3D multi-mass chromatograms of the overall CER species, based on normal-phase liquid chromatography (NPLC) connected to electrospray ionization-mass spectrometry (ESI-MS) using a gradient elution system and a postcolumn addition of a volatile salt-containing polar solvent. The CERs targeted from the 3D chromatograms were structurally analyzed using NPLC-ESI-tandem mass spectrometry (MS/MS), which resulted in the identification of 342 CER species in the inner forearm SC. This led to the discovery of a new CER class consisting of alpha-hydroxy fatty acid and dihydrosphingosine moieties, in addition to the 10 classes generally known. The results also revealed that those CERs contain long-chain (more than C(18))-containing sphingoids and a great number of isobaric species. These novel results will contribute not only to physiochemical research on CERs in the SC but also to lipidomics approaches to CERs in the skin.
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              Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis.

              I review how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and antimicrobial defense in patients with atopic dermatitis (AD). Although best known are mutations in filaggrin (FLG), mutations in other member of the fused S-100 family of proteins (ie, hornerin [hrn] and filaggrin 2 [flg-2]); the cornified envelope precursor (ie, SPRR3); mattrin, which is encoded by TMEM79 and regulates the assembly of lamellar bodies; SPINK5, which encodes the serine protease inhibitor lymphoepithelial Kazal-type trypsin inhibitor type 1; and the fatty acid transporter fatty acid transport protein 4 have all been linked to AD. Yet these abnormalities often only predispose to AD; additional acquired stressors that further compromise barrier function, such as psychological stress, low ambient humidity, or high-pH surfactants, often are required to trigger disease. T(H)2 cytokines can also compromise barrier function by downregulating expression of multiple epidermal structural proteins, lipid synthetic enzymes, and antimicrobial peptides. All of these inherited and acquired abnormalities converge on the lamellar body secretory system, producing abnormalities in lipid composition, secretion, and/or extracellular lamellar membrane organization, as well as antimicrobial defense. Finally, I briefly review therapeutic options that address this new pathogenic paradigm.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Project administrationRole: Supervision
                Role: InvestigationRole: Methodology
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 January 2019
                2019
                : 14
                : 1
                : e0210013
                Affiliations
                [1 ] Department of Dermatology and Plastic Surgery, Akita University Graduate School of Medicine, Akita, Japan
                [2 ] Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
                [3 ] Department of Dermatology, Aso Iizuka Hospital, Fukuoka, Japan
                INSERM, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8453-1313
                http://orcid.org/0000-0003-4767-9156
                Article
                PONE-D-18-17951
                10.1371/journal.pone.0210013
                6319710
                30608955
                3889c106-a110-4fca-811f-a17646c0455e
                © 2019 Chiba et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 June 2018
                : 14 December 2018
                Page count
                Figures: 4, Tables: 1, Pages: 13
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Allergies
                Allergic Diseases
                Atopic Dermatitis
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Allergies
                Allergic Diseases
                Atopic Dermatitis
                Medicine and Health Sciences
                Immunology
                Clinical Immunology
                Allergies
                Allergic Diseases
                Atopic Dermatitis
                Medicine and Health Sciences
                Dermatology
                Eczema
                Atopic Dermatitis
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Body Limbs
                Arms
                Forearms
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Body Limbs
                Arms
                Forearms
                Biology and Life Sciences
                Biochemistry
                Lipids
                Research and Analysis Methods
                Chromatographic Techniques
                Liquid Chromatography
                Liquid Chromatography-Mass Spectrometry
                Physical Sciences
                Chemistry
                Analytical Chemistry
                Mass Spectrometry
                Liquid Chromatography-Mass Spectrometry
                Research and Analysis Methods
                Spectrum Analysis Techniques
                Mass Spectrometry
                Liquid Chromatography-Mass Spectrometry
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fatty Acids
                Linoleic Acid
                Medicine and Health Sciences
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Clinical Laboratories
                Biology and Life Sciences
                Biochemistry
                Lipids
                Lipid Structure
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Ethers
                Epoxides
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Ethers
                Epoxides
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                All relevant data are within the manuscript and its Supporting Information files.

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