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      Surface Lipids as Multifunctional Mediators of Skin Responses to Environmental Stimuli

      1 , * , 2, 3

      Mediators of Inflammation

      Hindawi Publishing Corporation

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          Abstract

          Skin surface lipid (SSL) film is a mixture of sebum and keratinocyte membrane lipids, protecting skin from environment. Its composition is unique for the high percentage of long chain fatty acids, and of the polyterpenoid squalene, absent in other human tissues, and in non-human Primates sebum. Here, the still incomplete body of information on SSL as mediators of external chemical, physical, and microbial signals and stressors is revised, focusing on the central event of the continuous oxidative modification induced by the metabolic activity of residential and pathological microbial flora, natural or iatrogenic UV irradiation, exposure to chemicals and cosmetics. Once alpha-tocopherol and ubiquinol-10 antioxidant defences of SSL are overcome, oxidation of squalene and cholesterol gives rise to reactive by-products penetrating deeper into skin layers, to mediate local defensive inflammatory, photo-protective, immune reactions or, at higher concentrations, inducing local but also systemic immune depression, ultimately implicating skin cancerogenesis. Qualitative modifications of SSL represent a pathogenetic sign of diagnostic value in dermatological disorders involving altered sebum production, like pytiriasis versicolor, acne, atopic or seborrheic dermatitis, as well as photo-aging. Achievements of nutriceutical interventions aimed at restoring normal SSL composition and homeostasis are discussed, as feasible therapeutic goals and major means of photo-protection.

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          Most cited references 133

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          Stratum corneum defensive functions: an integrated view.

          Most epidermal functions can be considered as protective, or more specifically, as defensive in nature. Yet, the term "barrier function" is often used synonymously with only one such defensive function, though arguably its most important, i.e., permeability barrier homeostasis. Regardless of their relative importance, these protective cutaneous functions largely reside in the stratum corneum (SC). In this review, I first explore the ways in which the multiple defensive functions of the SC are linked and interrelated, either by their shared localization or by common biochemical processes; how they are co-regulated in response to specific stressors; and how alterations in one defensive function impact other protective functions. Then, the structural and biochemical basis for these defensive functions is reviewed, including metabolic responses and signaling mechanisms of barrier homeostasis. Finally, the clinical consequences and therapeutic implications of this integrated perspective are provided.
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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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              Photosensitized oxidation of membrane lipids: reaction pathways, cytotoxic effects, and cytoprotective mechanisms.

              Unsaturated lipids in cell membranes, including phospholipids and cholesterol, are well-known targets of oxidative modification, which can be induced by a variety of stresses, including ultraviolet A (UVA)- and visible light-induced photodynamic stress. Photodynamic lipid peroxidation has been associated with pathological conditions such as skin phototoxicity and carcinogenesis, as well as therapeutic treatments such as antitumor photodynamic therapy (PDT). Lipid hydroperoxides (LOOHs), including cholesterol hydroperoxides (ChOOHs), are important non-radical intermediates of the peroxidative process which can (i) serve as in situ reporters of type I vs. type II chemistry; (ii) undergo one-electron or two-electron reductive turnover which determines whether peroxidative injury is respectively intensified or suppressed; and (iii) mediate signaling cascades which either fortify antioxidant defenses of cells or evoke apoptotic death if oxidative pressure is too great. The purpose of this article is to review current understanding of photodynamic (UVA- or visible light-induced) lipid peroxidation with a special focus on LOOH generation and reactivity. Future goals in this area, many of which depend on continued development of state-of-the-art analytical techniques, will also be discussed.
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                Author and article information

                Journal
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2010
                20 October 2010
                : 2010
                Affiliations
                1Laboratory of Tissue Engineering and Skin Pathophysiology, Istituto Dermopatico dell'Immacolata (IDI IRCCS), Via Monti di Creta 104, 00167 Rome, Italy
                2Department of Food and Nutrition, Research Institute of Human Ecology, Kyung Hee University, Seoul 130-701, Republic of Korea
                3Department of Biomedical Sciences, University of Siena, 53100 Siena, Italy
                Author notes
                *Chiara De Luca: c.deluca@ 123456idi.it

                Academic Editor: Philip W. Wertz

                Article
                10.1155/2010/321494
                2963132
                20981292
                Copyright © 2010 C. De Luca and G. Valacchi.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review Article

                Immunology

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