Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition.

Background: The barrier dysfunction in atopic dermatitis (AD) skin correlates with stratum corneum (SC) lipid abnormalities including reduction of global lipid content, shorter ceramide (CER) as well as free fatty acid (FFA) chain length and altered CER subclass levels. However, the underlying cause of these changes in lipid composition has not been fully investigated.

Aim: We investigated whether the expression of CER and FFA biosynthesis enzymes are altered in AD skin compared with control skin and determine whether changes in enzyme expression can be related with changes in lipid composition.

Diverse regulation of claudin-1 and claudin-4 in atopic dermatitis.

Tight junctions are important for skin barrier function. The tight junction protein claudin 1 (Cldn-1) has been reported to be down-regulated in nonlesional skin of atopic dermatitis (AD) patients. In contrast, we did not observe a significant down-regulation of Cldn-1 in nonlesional skin of the AD cohort used in this study.

Explant cultures of atopic dermatitis biopsies maintain their epidermal characteristics in vitro.

Atopic dermatitis (AD) is a common inflammatory skin disorder characterised by various epidermal alterations. Filaggrin (FLG) mutations are a major predisposing factor for AD and much research has been focused on the FLG protein. Human skin equivalents (HSEs) might be useful tools for increasing our understanding of FLG in AD and to provide a tool for the screening of new therapies aimed at FLG replacement.

Exploring the potentials of nurture: 2(nd) and 3(rd) generation explant human skin equivalents.

Background: Explant human skin equivalents (Ex-HSEs) can be generated by placing a 4mm skin biopsy onto a dermal equivalent. The keratinocytes migrate from the biopsy onto the dermal equivalent, differentiate and form the epidermis of 1(st) generation Ex-HSEs. This is especially suitable for the expansion of skin material from which only small fragments of skin can be harvested e.

An ex vivo human skin model for studying skin barrier repair.

In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique. After stripping the explants, they were cultured in vitro to allow the regeneration of the SC.

Barrier properties of an N/TERT-based human skin equivalent.

Human skin equivalents (HSEs) can be considered a valuable tool to study aspects of human skin, including the skin barrier, or to perform chemical or toxicological screenings. HSEs are three-dimensional skin models that are usually established using primary keratinocytes and closely mimic human skin. The use of primary keratinocytes has several drawbacks, including a limited in vitro life span and large donor-donor variation.

TNF-α and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents.

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which the skin barrier function is disrupted. In this inflammatory AD environment, cytokines are upregulated, but the cytokine effect on the AD skin barrier is not fully understood. We aimed to investigate the influence of Th2 (IL-4, IL-13, IL-31) and pro-inflammatory (tumor necrosis factor alpha (TNF-α)) cytokines on epidermal morphogenesis, proliferation, differentiation, and stratum corneum lipid properties.

Knock-down of filaggrin does not affect lipid organization and composition in stratum corneum of reconstructed human skin equivalents.

Human skin mainly functions as an effective barrier against unwanted environmental influences. The barrier function strongly relies on the outermost layer of the skin, the stratum corneum (SC), which is composed of corneocytes embedded in an extracellular lipid matrix. The importance of a proper barrier function is shown in various skin disorders such as atopic dermatitis (AD), a complex human skin disorder strongly associated with filaggrin (FLG) null mutations, but their role in barrier function is yet unclear.

Nature versus nurture: does human skin maintain its stratum corneum lipid properties in vitro?

Human skin equivalents (HSEs) mimic human skin closely, but show differences in their stratum corneum (SC) lipid properties. The aim of this study was to determine whether isolation of primary cells, which is needed to generate HSEs, influence the SC lipid properties of HSEs. For this purpose, we expanded explants of intact full thickness human skin and isolated epidermal sheets in vitro.