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      Deficient Production of Hexadecenoic Acid in the Skin Is Associated in Part with the Vulnerability of Atopic Dermatitis Patients to Colonization by Staphylococcus aureus

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          Abstract

          Background and Objectives: As one of the major skin fatty acids, cis-6-hexadecenoic acid (C16:1Δ6) exhibits a specific antibacterial activity and might play a specific role in the defense mechanism against Staphylococcus aureus, in healthy subjects whereas S. aureus frequently colonizes the skin of patients with atopic dermatitis (AD). Methods: Fatty acid composition of sebum at the recovery level was analyzed by gas chromatography and S. aureus colonizing the skin was assessed by the ‘cup-scrub’ method (9 patients and 10 healthy controls). To evaluate in vivo effect of C16:1Δ6 on colonization, C16:1Δ6 was applied for 2 weeks on the upper arm skin of another group of AD patients (11 patients). Results: Analysis of sebum lipids revealed that there is a significant lower free C16:1Δ6 content in nonlesional skin from AD patients compared with healthy controls. This lower content is also accompanied by a significantly lower level of C16:1Δ6 in the total fatty acid composition of sebum (analyzed following hydrolysis). The lower level of free C16:1Δ6 correlated significantly (R<sup>2</sup> = 0.41, p < 0.01) with the numbers of S. aureus colonizing nonlesional skin. Topical application of free C16:1Δ6 on the skin of AD patients for 2 weeks abolished the markedly increased bacterial count in 6 out of the 8 AD patients tested. Conclusions: Free C16:1Δ6 may be involved in the defense mechanism against S. aureus in healthy skin and this deficit triggers the susceptibility of the skin to colonization by S. aureus in AD.

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          Most cited references16

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          Skin lipids: their biochemical uniqueness.

          Two key words characterize the uniqueness of skin lipids: complexity and perversity. Each suggests a function. Complexity manifests itself in the large number and variety of both saturated and unsaturated fatty chains synthesized by human skin. Functionally, this allows each individual to have a distinct odor or chemical fingerprint. Perversity manifests itself when one compares the lipids synthesized by skin with those synthesized by internal tissues. For example, skin makes odd instead of only even chains, branched instead of only straight chains, free instead of only esterified acids, places double bonds in unusual positions in the fatty chains, extends chains to extreme lengths, and accumulates intermediates in the synthesis of a biologically valuable compound such as cholesterol. Functionally, these products may pose metabolic problems to potential pathogens and thus contribute to the survival of only compatible microorganisms.
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            Decreased Level of Ceramides in Stratum Corneum of Atopic Dermatitis: An Etiologic Factor in Atopic Dry Skin?

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              Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus.

              The stratum corneum of the skin of patients with atopic dermatitis is highly susceptible to colonization by various bacteria, including Staphylococcus aureus. The defense system of the skin against bacterial invasion appears to be significantly disrupted in atopic dermatitis skin, but little is known about the defense mechanism(s) involved. As one sphingolipid metabolite, sphingosine is known to exert a potent antimicrobial effect on S. aureus at physiologic levels, and it may play a significant role in bacterial defense mechanisms of healthy normal skin. Because of the altered ceramide metabolism in atopic dermatitis, the possible alteration of sphingosine metabolism might be associated with the acquired vulnerability to colonization by S. aureus in patients with atopic dermatitis. In this study, we measured the levels of sphingosine in the upper stratum corneum from patients with atopic dermatitis, and then compared that with the colonization levels of bacteria in the same subjects. Levels of sphingosine were significantly downregulated in uninvolved and in involved stratum corneum of patients with atopic dermatitis compared with healthy controls. This decreased level of sphingosine was relevant to the increased numbers of bacteria including S. aureus present in the upper stratum corneum from the same subjects. This suggests the possibility that the increased colonization of bacteria found in patients with atopic dermatitis may result from a deficiency of sphingosine as a natural antimicrobial agent. As for the mechanism involved in the decreased production of sphingosine in atopic dermatitis, analysis of the activities of ceramidases, major sphingosine-producing enzymes, revealed that, whereas the activity of alkaline ceramidase did not differ between patients with atopic dermatitis and healthy controls, the activity of acid ceramidase was significantly reduced in patients with atopic dermatitis and this had obvious relevance to the increased colonization of bacteria in those subjects. Further, there was a close correlation between the level of sphingosines and acid ceramidase (r = 0.65, p < 0.01) or ceramides (r = 0.70, p < 0.01) in the upper stratum corneum from the same patients with atopic dermatitis. Collectively, our results suggest the possibility that vulnerability to bacterial colonization in the skin of patients with atopic dermatitis is associated with reduced levels of a natural antimicrobial agent, sphingosine, which results from decreased levels of ceramides as a substrate and from diminished activities of its metabolic enzyme, acid ceramidase.
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                Author and article information

                Journal
                DRM
                Dermatology
                10.1159/issn.1018-8665
                Dermatology
                S. Karger AG
                1018-8665
                1421-9832
                2005
                October 2005
                04 November 2005
                : 211
                : 3
                : 240-248
                Affiliations
                aBiological Science Laboratories and bAnalytical Research Center, Kao Corporation, Tochigi, cDepartment of Dermatology, Jichi Medical University, Tochigi, Japan
                Article
                87018 Dermatology 2005;211:240–248
                10.1159/000087018
                16205069
                32f19a67-7ec1-4430-b44f-8f8bac527d68
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 21 October 2004
                : 04 January 2005
                Page count
                Figures: 5, References: 22, Pages: 9
                Categories
                Clinical and Laboratory Investigations

                Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Atopic dermatitis,Staphylococcus aureus,Skin surface lipids,Antibacterial activity,cis-6-Hexadecenoic acid

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