br Introduction The epidermal permeability barrier is one of
Introduction The epidermal permeability barrier is one of the most crucial protective functions of the skin and is primarily mediated by stratum corneum lipids and differentiation-related proteins. Stratum corneum lipids consist mainly of an equal molar ratio of cholesterol, fatty acids, and ceramides. The major differentiation-related proteins include filaggrin, involucrin, and loricrin. Alteration of either epidermal lipid metabolism or epidermal differentiation can affect permeability barrier function. Conversely, permeability barrier requirements regulate a wide range of epidermal metabolic processes, including epidermal proliferation, differentiation, lipid production, oxidative stress, as well as antimicrobial defense. Moreover, the role of the epidermal permeability barrier in regulating cutaneous inflammation has been well demonstrated by our group and others. Recent studies have indicated that permeability barrier function is closely associated with the development of certain inflammatory skin disorders accompanied by permeability barrier abnormalities, such as atopic dermatitis, contact dermatitis, and psoriasis. Improving epidermal permeability barrier function has proved effective in treating atopic dermatitis. Additionally, preventive benefits of enhancing permeability barrier function for atopic dermatitis have also been demonstrated. However, the importance of enhancing permeability barrier function in the management of atopic eczema is still undervalued. In this article, we review the benefits of enhancing permeability barrier strategies in atopic eczema.
Regulatory role of the epidermal permeability barrier in cutaneous inflammation Clinically, inflammatory dermatoses often exhibit a defective permeability barrier. Although it is not clear whether a primary immunologic defect results in defective barrier or vice versa, it is clear that barrier disruption stimulates cytokine production and release. Tumor necrosis factor (TNF) α is expressed primarily in the upper order eicosapentaenoic acid in normal mouse skin. After acute barrier disruption with either acetone or tape-stripping, TNFα expression increases throughout all of the nucleated epidermal cell layers. This increase in TNFα expression, as well as several other keratinocyte-derived cytokines, occurs as early as 2 hours after acute barrier disruption. Likewise, TNFα expression is also increased in the epidermis of essential fatty acid deficient (EFAD) mice, which display a defective permeability barrier. Consistent with TNFα protein expression, the expression levels of TNFα mRNA are maximally increased (> 20-fold) 1 hour after acute barrier disruption and return to normal levels by 8 hours. Moreover, the expression levels of mRNA for TNF p55 receptor are also upregulated in acute barrier abrogation with either acetone or tape-stripping, and in EFAD mice. By contrast, barrier abrogation does not alter the expression levels of epidermal TNFβ mRNA. Although barrier abrogation increases TNFα expression, artificial restoration of the permeability barrier with a vapor impermeable membrane does not prevent the increase in expression levels of either protein or mRNA for TNFα in acetone-treated and normal skin. However, in chronic inflammation, such as occurs in EFAD mice, occlusion with a vapor impermeable membrane lowers epidermal interleukin-1 (IL-1)α and TNFα mRNA levels. IL-1α is another major proinflammatory cytokine in the skin. Acute barrier disruption increases IL-1α expression in both the dermis and epidermis 10 minutes after tape-stripping and returns to normal levels by 24 hours. Similarly, a higher expression level of IL-1α exists in both the dermis and epidermis of EFAD mice. In contrast to TNFα, occlusion of normal skin for 48 hours decreases epidermal IL-1α expression. Additionally, following tape-stripping, the expression levels of epidermal IL-1α are lower in preoccluded than nonoccluded mouse skin. Tape-stripping-induced increases in IL-1α expression are likely to be released from a preformed pool, because the expression levels of epidermal IL-1α at room temperature are comparable to that at 4°C. Ito et al reported that UVB irradiation of barrier-disrupted skin enhanced the expression of IL-1β by Langerhans cells. These results suggest that the impact of the permeability barrier on cytokine expression varies with the type of cytokine. Upregulation of epidermal mRNA for cytokines was also demonstrated in humans. It is worth noting that following tape-stripping of mouse skin, mRNA levels for IFNγ remained unchanged in mouse epidermis, while they increase significantly in humans. The influences of the permeability barrier on cytokine expression are summarized in Table 1.