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Journal ArticleDOI

The skin: an indispensable barrier

Ehrhardt Proksch, +2 more
- 01 Dec 2008 - 
- Vol. 17, Iss: 12, pp 1063-1072
TLDR
Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis.
Abstract
The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis

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Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes.

TL;DR: PDE4B has a role in the mechanism of BP‐3‐induced phototoxicity, and its association with the upregulation of pro‐inflammatory mediators and the downregulation of epidermal differentiation markers were confirmed in a reconstituted three dimensional human epidermis model.
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Responses of Reconstructed Human Epidermis to Trichophyton rubrum Infection and Impairment of Infection by the Inhibitor PD169316.

TL;DR: Intriguingly, among several p38 mitogen-activated protein kinase inhibitors, PD169316 alone was able to inhibit growth of T. rubrum on Sabouraud agar and to suppress the process of infection on RHE, suggesting that PD16 9316 acts on a specific target in dermatophytes themselves.
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References
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Journal ArticleDOI

The cornified envelope: a model of cell death in the skin

TL;DR: New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing the understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
Journal ArticleDOI

Claudin-based tight junctions are crucial for the mammalian epidermal barrier a lesson from claudin-1–deficient mice

TL;DR: Findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin.
Journal ArticleDOI

Claudins and epithelial paracellular transport.

TL;DR: Information is reviewed on the structure, function, and transcriptional and posttranslational regulation of the claudin family as well as of their evolutionarily distant relatives called the PMP22/EMP/MP20/claudin, or pfam00822, superfamily.
Journal ArticleDOI

Barrier Function of the Skin: “La Raison d'Être” of the Epidermis

TL;DR: More sophisticated understanding of epidermal barrier function will lead to more rational therapy of a host of skin conditions in which the barrier is impaired, current work has focused on developing a more physiologic mix of lipids for topical application to skin.
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Trending Questions (1)
How do skin be a physical barrier ?

The skin forms a physical barrier through components such as protein-enriched cells, lipid-enriched intercellular domains, and tight junctions, preventing the invasion of pathogens and the loss of water and solutes.