Role of the epidermal barrier in atopic dermatitis

The skin's permeability barrier protects against extensive water loss and prevents the entry into the skin of harmful substances like irritants, allergens and microorganisms. The permeability barrier is mainly located in the stratum corneum and consists of corneocytes and a lipid‐enriched intercellular domain. The barrier is formed during epidermal differentiation. In atopic dermatitis the skin barrier is disturbed already in non‐lesional skin. The disturbed skin barrier allows the entry of environmental allergens from house dust mites, animal dander and grass pollen into the skin. In predisposed individuals these allergens may trigger via immunologic pathways the inflammation of atopy. The causes for the disturbed epidermal skin barrier are changes in skin lipids and in epidermal differentiation, in particular filaggrin mutations. Filaggrin mutations lead to a disturbed skin barrier and dry skin which are hallmarks in atopic dermatitis. Therapeutic agents influence the skin barrier differently; topical therapy with potent corticosteroids does not lead to the repair of the barrier in atopic dermatitis, whereas therapy with the calcineurin inhibitors and lipid‐containing emulsions support barrier repair.     

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. To study the role of FLG in SC barrier properties in terms of SC lipid organization and lipid composition, we generated an N/TERT‐based 3D‐skin equivalent (NSE) after knock‐down of FLG with shRNA. In these NSEs, we examined epidermal morphogenesis by evaluating the expression of differentiation markers keratin 10, FLG, loricrin and the proliferation marker ki67. Furthermore, the SC was extensively analysed for lipid organization, lipid composition and SC permeability. Our results demonstrate that FLG knock‐down (FLG‐KD) did not affect epidermal morphogenesis, SC lipid organization, lipid composition and SC permeability for a lipophilic compound in NSEs. Therefore, our findings indicate that FLG‐KD alone does not necessarily affect the functionality of a proper barrier function.     

Barrier function of the skin: "la raison d'être" of the epidermis

The primary function of the epidermis is to produce the protective, semi-permeable stratum corneum that permits terrestrial life. The barrier function of the stratum corneum is provided by patterned lipid lamellae localized to the extracellular spaces between corneocytes. Anucleate corneocytes contain keratin filaments bound to a peripheral cornified envelope composed of cross-linked proteins. The many layers of these specialized cells in the stratum corneum provide a tough and resilient framework for the intercellular lipid lamellae. The lamellae are derived from disk-like lipid membranes extruded from lamellar granules into the intercellular spaces of the upper granular layer. Lysosomal and other enzymes present in the extracellular compartment are responsible for the lipid remodeling required to generate the barrier lamellae as well as for the reactions that result in desquamation. Lamellar granules likely originate from the Golgi apparatus and are currently thought to be elements of the tubulo-vesicular trans-Golgi network. The regulation of barrier lipid synthesis has been studied in a variety of models, with induction of several enzymes demonstrated during fetal development and keratinocyte differentiation, but an understanding of this process at the molecular genetic level awaits further study. Certain genetic defects in lipid metabolism or in the protein components of the stratum corneum produce scaly or ichthyotic skin with abnormal barrier lipid structure and function. The inflammatory skin diseases psoriasis and atopic dermatitis also show decreased barrier function, but the underlying mechanisms remain under investigation. Topically applied "moisturizers" work by acting as humectants or by providing an artificial barrier to trans-epidermal water loss; current work has focused on developing a more physiologic mix of lipids for topical application to skin. Recent studies in genetically engineered mice have suggested an unexpected role for tight junctions in epidermal barrier function and further developments in this area are expected. Ultimately, 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.     

Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair

Background Recent studies have emphasized the importance of heritable and acquired skin barrier abnormalities in common inflammatory diseases such as psoriasis and atopic dermatitis (AD). To date, no comprehensive studies on the effect of experimental barrier disruption on cornified envelope protein expression have been performed. Objectives To analyse the effect of experimental skin barrier disruption on the expression of cornified envelope structural proteins and keratinocyte differentiation‐regulating proteins. Methods We examined mRNA (day 1, 3 and 7) and protein (day 1, 2, 4 and 9) expression levels of structural proteins and regulatory molecules after sodium dodecyl sulphate (SDS) application on normal skin, and tape stripping of uninvolved epidermis of patients with psoriasis and AD and healthy controls. Results Upon tape stripping, several structural molecules were significantly downregulated (at the mRNA level as well as the protein level), including LCE5A, LCE2B, FLG, FLG2 and LOR, whereas others were upregulated: IVL, SPRR1, SPRR2, HRNR and most notably LCE3A. The epidermal crosslinking enzymes TGM1, TGM3 and TGM5 were all upregulated, whereas proteases involved in the desquamation process (CTSV, KLK5 and KLK7) were downregulated or unaffected. Most results were similar in SDS‐instigated irritant contact dermatitis. There was no significant difference in response between normal epidermis and nonlesional skin of patients with psoriasis and AD. Conclusions Skin barrier disruption induces a temporary barrier repair response composed of increased expression of several cornification‐related proteins, and decreased expression of some structural and desquamation‐related proteins.     

皮肤屏障功能研究进展

皮肤屏障主要由角化包膜和脂质膜、中间丝聚合蛋白、角蛋白、角化桥粒、板层小体和角质层角质形成细胞问质、紧密连接等组成,防止水分的丢失及阻止外界的侵害,维持机体内稳态.基因突变、变应原、微生物、紫外线等因素共同作用下,能导致皮肤屏障结构、代谢及功能的异常,引起鱼鳞病、特应性皮炎等皮肤病.阐明皮肤病与屏障结构及功能异常联系,指导开发有效的诊疗和预防措施.     

Functional analyses of the skin surface of the areola mammae: comparison between healthy adult male and female subjects and between healthy individuals and patients with atopic dermatitis

Background Although the nipple and areola of the breast constitute a unique and prominent area on the chest, so far no study has been done on the functional properties of their skin surfaces. Objective To study the stratum corneum (SC) covering the areola using noninvasive methods. Methods Eighteen adult healthy subjects comprising nine men and nine women and 18 age‐ and sex‐matched patients with atopic dermatitis (AD), none of whom had visible skin lesions, participated in the study. Transepidermal water loss (TEWL), skin surface hydration and skin surface lipid levels were measured on the areola and adjacent breast skin. The size of the skin surface corneocytes of these skin regions was assessed. Results All the healthy subjects showed significantly higher TEWL accompanied by smaller sized corneocytes on the areola than on the adjacent breast skin. Only female subjects revealed a significantly higher skin surface hydration state together with significantly increased skin surface lipid levels on the areola than on the adjacent breast skin. These sex differences were observed even in patients with AD. Comparison between healthy individuals and the patients with AD demonstrated higher TEWL, decreased skin surface hydration state and lower skin surface lipid levels associated with smaller sized corneocytes in the areola in the patients with AD, especially in male patients. Conclusions In adults, the SC barrier function and SC water‐binding capacity of the areola were functionally poorer than in the adjacent skin, being covered by smaller sized corneocytes and lower amounts of skin surface lipids, especially in men and in patients with AD.     

Aging of the skin barrier

The skin barrier is mainly present in the stratum corneum (SC), composed of corneocytes surrounded by intercellular lipid lamellae, and attached by corneodesmosome. The tight junction attached to the lateral walls of keratinocytes in the upper part of the stratum granulosum is also included in the skin barrier. During aging, the following structures and functions of the skin barrier are changed or disturbed: (1) skin barrier structure, (2) permeability barrier function, (3) epidermal calcium gradient, (4) epidermal lipid synthesis and SC lipid processing, (5) cytokine production and response after insults, (6) SC acidity, (7) SC hydration, and (8) antimicrobial barrier. Patients with diabetes also show changes in the skin barrier similar to those in aged skin, and the characteristics of the skin barrier are very similar. Understanding the pathogenic mechanisms of the skin barrier in aging will permit us to develop therapeutic strategies for aged or diabetic skin.     

Noninvasive biophysical assessments of the efficacy of a moisturizing cosmetic cream base for patients with atopic dermatitis during different seasons

BACKGROUND: The use of emollients is recommended for patients with atopic dermatitis (AD) to maintain improved condition. OBJECTIVES: To ascertain objectively the effectiveness of a moisturizing cream for patients with AD during different seasons. METHODS: We conducted clinical evaluations, noninvasive biophysical measurements and biochemical analyses of the stratum corneum (SC) components of the volar forearm skin of 23 patients with AD after a moisturizer was applied twice daily for 4 weeks. The moisturizer was formulated according to the consensus of cosmetic scientists belonging to major Japanese cosmetic companies. The nontreated forearm served as a control. RESULTS: After using the moisturizer treatment, the hydration of the SC significantly increased together with a decrease in the desquamation measurements and an improvement in the regularity of skin surface corneocytes. An improvement was observed in the SC barrier function in winter, but was achieved only after 4 weeks in late spring during which time there even occurred exacerbation of skin conditions in three patients. With use of the moisturizer treatment, we found no change in the SC content of free amino acids or ceramides, the ratio of interleukin (IL)-1 receptor antagonist to IL-1alpha, the ratio of immature to mature cornified envelopes, the size of the corneocytes or the emergence of parakeratotic cells in the skin surface corneocytes. CONCLUSION: Treatment with an adequate moisturizer is beneficial for the dry skin of patients with AD during the dry, cold season but it does not influence the impaired SC barrier function as effectively in the less arid season.     

Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity

Although many skin disorders, including psoriasis and atopic dermatitis, are adversely affected by psychologic stress (PS), the pathophysiologic link between PS and disease expression remains unclear. Recent studies demonstrated PS-induced alterations in permeability barrier homeostasis, mediated by increased endogenous glucocorticoids. Here, we assessed the mechanisms by which PS alters stratum corneum (SC) function. Insomniac psychologic stress (IPS) altered both barrier homeostasis and SC integrity. IPS decreased epidermal cell proliferation, impaired epidermal differentiation, and decreased the density and size of corneodesmosomes (CD), which was linked to degradation of CD proteins (e.g., desmoglein1). Barrier compromise was linked to decreased production and secretion of lamellar bodies (LB), which in turn could be attributed to a decrease in de novo synthesis of epidermal lipids. Topical physiologic lipids (equimolar cholesterol, ceramides, and free fatty acids) normalized both barrier homeostasis and SC integrity in IPS mice, further evidence that lipid deficiency accounted for these functional abnormalities. Thus, PS inhibition of epidermal lipid synthesis results in decreased LB formation and secretion, as well as decreased CD, compromising both permeability barrier homeostasis and SC integrity. These studies suggest that topical treatment with epidermal physiologic lipids could be beneficial in stress-induced, barrier-associated dermatoses, such as psoriasis and atopic dermatitis.     

Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis

A defective permeability barrier leads to the penetration of environmental allergens into the skin and initiates immunological reactions and inflammation crucially involved in the pathogenesis of atopic dermatitis (AD). Decreased stratum corneum ceramide content may cause the defect in permeability barrier function consistently found in AD. Acid and neutral sphingomyelinase (A- and N-SMase) generate ceramides with structural and signal transduction functions in epidermal proliferation and differentiation. We determined epidermal SMase activities, DNA synthesis, involucrin, loricrin, filaggrin, and keratin expression in lesional and non-lesional skin of AD patients. We found decreased epidermal A-SMase activity in lesional and non-lesional skin, correlating with reduced stratum corneum ceramide content and disturbed barrier function. N-SMase activity was reduced in non-lesional skin and more significantly reduced in lesional skin, correlating with impaired expression of cornified envelope proteins and keratins, important for skin barrier function. Changes in involucrin, loricrin, filaggrin, keratin K 5 (basal) and K 16 (proliferation associated) were noticed in non-lesional and lesional skin, whereas changes in K 10 (suprabasal), K 6 (proliferation associated), and K 17 (inflammation associated) were found only in lesional skin. In summary, reduction in SMase-generating ceramides and impaired differentiation are involved in the defective barrier function found in AD.     

Skin barrier function, epidermal proliferation and differentiation in eczema

Skin permeability barrier function is impaired in eczema, particularly in contact and atopic dermatitis (AD). In contact dermatitis disruption of the barrier by irritants and allergens is the primary event, followed by sensitization, inflammation, increased epidermal proliferation and changes in differentiation. Genetically impaired skin barrier function is already present in non-lesional and more pronounced in lesional skin in AD. Increased epidermal proliferation and disturbed differentiation, including changes in lipid composition, cause impaired barrier function in AD. Defective permeability barrier function enables the enhanced penetration of environmental allergens into the skin and initiates immunological reactions and inflammation. Barrier dysfunction is therefore crucially involved in the pathogenesis of AD. The atopic syndrome represents a genetically impaired skin barrier function as well as impaired nasal, bronchial, and intestinal mucous membranes leading to AD, allergic rhinitis, bronchial asthma or aggravation of AD. Common treatment strategies for eczema include the application of lipid-based creams and ointments, which aim toward the restoration of the defective permeability barrier, thus helping to normalize proliferation and differentiation.     

pH in nature,humans and skin

The pH plays an important physiological role in nature and humans. pH varies from 1 to 8 in human organs with tight regulation in blood and epithelia of barrier organs. The physiological pH of the stratum corneum is 4.1–5.8 and several mechanisms contribute to its formation: filaggrin degradation, fatty acid content, sodium‐hydrogen exchanger (NHE1) activation and melanosome release. First, the acidic pH of the stratum corneum was considered to present an antimicrobial barrier preventing colonization (e.g. by Staphylococcus aureus and Malassezia). Later on, it was found that the pH influences skin barrier function, lipid synthesis and aggregation, epidermal differentiation and desquamation. Enzymes of ceramide metabolism (e.g. β‐glucocerebrosidase or acid sphingomyelinase) as well as proteases (e.g. chymotryptic enzyme or cathepsin D linked to epidermal differentiation and desquamation) are regulated by the pH. Experimental disruption of the physical barrier leads to an increase of pH, returning to normal levels only after many hours. Inflammatory skin diseases and diseases with an involvement of the epidermis exhibit a disturbed skin barrier and an increased pH. This is known for atopic dermatitis, irritant contact dermatitis, ichthyosis, rosacea and acne, but also for aged and dry skin. Normalizing the pH by acidification through topical treatment helps to establish a physiological microbiota, to repair skin barrier, to induce epidermal differentiation and to reduce inflammation.     

The effect of wet-wrap dressing on epidermal barrier in patients with atopic dermatitis

BACKGROUND: Wet-wrap dressing has been shown to be effective for atopic dermatitis; however, the therapeutic mechanism of wet-wrap dressing is only the hypothesis based on the recovery of decreased epidermal barrier function. OBJECTIVES: To examine the therapeutic efficacy as well as the mechanism of wet-wrap dressing in atopic dermatitis patients. METHODS: To examine the difference of non-lesional and lesional atopic skin and to evaluate the change between epidermal barrier function before and after the treatment, SCORAD, epidermal water content, transepidermal water loss, the lipid amount of skin surface, immunohistochemical staining of filaggrin and loricrin, transmission electron microscopic examination, and calcium ion capture cytochemistry method were done in 10 severe form atopic dermatitis patients. RESULTS: In atopic dermatitis patients, SCORAD was clearly decreased, epidermal water content was increased, and transepidermal water loss was decreased after wet-wrap dressing. After wet-wrap dressing, increased release of lamellar body and the recovery of the damaged lamellar structure of intercellular lipid were observed; nevertheless, neither the change in keratinocyte differentiation nor the change of calcium ion gradient was detected. A week after the termination of wet-wrap dressing, increased water content and decreased transepidermal water loss were still maintained. CONCLUSION: We confirmed the abnormality of the epidermal barrier in atopic dermatitis, and the effects of wet-wrap were associated with the recovery of epidermal barrier. In atopic lesions, wet-wrap dressing induced clinical improvement by the release of lamellar body and the restoration of intercellular lipid lamellar structure.     

The lipid alterations in the stratum corneum of dogs with atopic dermatitis are alleviated by topical application of a sphingolipid-containing emulsion

Background. Atopic dermatitis (AD) results from an altered skin barrier associated with defects in the lipid composition of the skin. Dogs with AD present similar clinical symptoms to humans, and may be a useful model for investigations into AD. Aim. To analyse the changes occurring in the lipids of the stratum corneum (SC) of dogs with AE after 3 weeks of topical treatment with an emulsion containing ceramides, free fatty acids (FFAs) and cholesterol (skin lipid complex; SLC). Methods. Nonlesional SC was collected by tape stripping from control and treated areas. Free and protein‐bound lipids were purified, and the various classes were isolated by column chromatography, analysed by thin‐layer chromatography and assayed. Results. Ceramides, FFA and cholesterol were all found to be lower in the skin of untreated dogs with AD than in normal dogs, and the topical treatment resulted in significantly increased values for ceramides. Conversely, only trace amounts of glucosylceramides were present in normal SC, but a high concentration (27 μg per mg protein) was detected in canine atopic SC, which disappeared after treatment with SLC. There was a heterogeneous distribution of all of the lipids in the different layers of canine atopic SC, which was more pronounced for protein‐bound than for free lipids. Following topical treatment, the protein‐bound lipid content normalized. Conclusions. Topical treatment with SLC resulted in a significant improvement of the lipid biosynthesis of keratinocytes in atopic dogs, thereby potentially enabling the formation of a tighter epidermal barrier.     

Atopic xerosis: employment of noninvasive biophysical instrumentation for the functional analyses of the mildly abnormal stratum corneum and for the efficacy assessment of skin care products

The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller-sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape-stripping, it produces a much more severe, long-lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water-soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal-looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water-holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring.     

Stratum corneum lipid profile and maturation pattern of corneocytes in the outermost layer of fresh scars: the presence of immature corneocytes plays a much more important role in the barrier dysfunction than do changes in intercellular lipids

BACKGROUND: The functional characteristics of the stratum corneum (SC) of fresh scars as well as keloids and hypertrophic scars are characterized by elevated transepidermal water loss (TEWL) and increased SC hydration. OBJECTIVES: To study the composition of the intercellular lipids and maturation properties of the cornified envelope (CE) of the SC, as these are the most important components for the SC barrier function in fresh scars. METHODS: SC lipids were extracted from the donor site for split-thickness skin grafting soon after re-epithelialization using a cup method, and were analysed with high-performance thin-layer chromatography. CEs, which were prepared from superficial layers of the SC, were double stained with Nile red and anti-involucrin. RESULTS: We found a significant decrease in the proportion of ceramide (CER) in the SC lipids of fresh scars. We also observed changes in the SC CER profile that consisted of an increase in CER 4 and CER 7 and a decrease in CER 3, without any significant change in the proportion of CER 1. These changes were insufficient to explain the remarkably high TEWL recorded in the early stage of fresh scars. In contrast, with double staining of CE with Nile red and anti-involucrin, we detected the presence of numerous immature and less hydrophobic corneocytes in the outermost layer of the SC of fresh scars. Scanning electron microscopy of such corneocytes revealed numerous fine wrinkles on their enlarged surface area. Most of all, we found a closely similar, time-dependent, exponential decrease in the ratio of immature corneocytes with a poorly hydrophobic CE and in the recorded TEWL values in fresh scars. There was a highly significant positive correlation between the proportion of immature corneocytes in the outermost layer of the SC and TEWL values. CONCLUSIONS: These results suggest that the SC barrier dysfunction of the fresh scars is attributable to the presence of immature corneocytes with a less hydrophobic CE, rather than to the changes in SC lipid composition.     

The management of dry skin with topical emollients – recent perspectives

Dry skin (xerosis) is a common symptom of a number of chronic skin diseases, such as atopic dermatitis, but can also be caused by environmental factors, such as cold weather and frequent showering. The condition can cause unsightliness of the skin, discomfort, itching, and can have a negative impact on patients' quality of life. This article will cover recent developments in the understanding of xerosis and its management with emollients. The stratum corneum consists of corneocytes and lipid‐enriched intercellular bilayers. These are both produced from keratinocytes in a process called epidermal differentiation. Disturbed epidermal differentiation, resulting in the impairment of stratum corneum intercellular lipid bilayers and natural moisturizing factor, is the root cause of xerosis. The constituent ingredients of emollients should, therefore, address the different factors that contribute to dry skin and, most importantly, attempt to restore epidermal differentiation. The use of lipids, physiological lipids, humectants and antipruritics will help to restore the lipid lamellae, improve skin hydration, skin elasticity and prevent itching. The ideal emollient will include these ingredients plus an agent to support epidermal differentiation. Selecting the correct emollient product and using it regularly are vital factors in the management of xerosis.     

The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients

An important feature of atopic eczema (AE) is a decreased skin barrier function. The stratum corneum (SC) lipids – comprised of ceramides (CERs), free fatty acids (FFAs) and cholesterol – fulfil a predominant role in the skin barrier function. In this clinical study, the carbon chain length distribution of SC lipids (FFAs and CERs) and their importance for the lipid organization and skin barrier function were examined in AE patients and compared with control subjects. A reduction in FFA chain length and an increase in unsaturated FFAs are observed in non‐lesional and lesional SC of AE patients. The reduction in FFA chain length associates with a reduced CER chain length, suggesting a common synthetic pathway. The lipid chain length reduction correlates with a less dense lipid organization and a decreased skin barrier function. All changes are more pronounced in lesional SC compared with non‐lesional skin. No association was observed between lipid properties and filaggrin mutations, an important predisposing factor for developing AE. The results of this study demonstrate an altered SC lipid composition and signify the importance of these changes (specifically regarding the CER and FFA chain lengths) for the impaired skin barrier function in AE. This provides insights into epidermal lipid metabolism as well as new opportunities for skin barrier repair.     

Membrane-coating granules in "dry" non-eczematous skin of patients with atopic dermatitis. A quantitative electron microscopic study

In recent years much interest has been focused on the functions of the membrane-coating granules (MCGs). These granules seem to play an essential role in the formation of the barrier of the stratum corneum by extruding their lipid-rich content into the extracellular space of the corneocytes. The dry non-eczematous skin in atopic dermatitis has been reported to have defective barrier function. In the present study a quantitative electron microscopic analysis was made of the volume of MCGs in the transition zone between the stratum granulosum and stratum corneum in dry skin of patients with atopic dermatitis. The relative volume of MCGs was significantly greater than that in normal skin. This finding may indicate a disturbance of the "maturation" of the MCGs, leading to a defect in the barrier function in atopic dermatitis.     

Barrier function, epidermal differentiation, and human beta-defensin 2 expression in tinea corporis

Tinea corporis is a superficial mycotic infection resulting in substantial epidermal changes. We determined skin barrier function, epidermal differentiation, and human-beta-defensin 2 (hBD-2) protein expression in 10 patients with tinea corporis caused by Trichophyton rubrum (T. rubrum). We found disturbed skin barrier function as shown by a significant increase in transepidermal water loss (TEWL) and specific ultrastructural changes including disturbed formation of extracellular lipid bilayers, lamellar body extrusion, and deposit of clotted material at the stratum granulosum/stratum corneum interface. Epidermal proliferation in tinea increased several fold and accordingly, proliferation and inflammation-associated keratins K6, K16, and K17 were expressed. Expression of basal keratins K5 and K14 increased, whereas differentiation-associated K10 was reduced. Reduction of the cornified envelope proteins involucrin, loricrin, and the S100 protein filaggrin was also seen. Reduced filaggrin expression correlated with reduced skin hydration; protein breakdown products of filaggrin have been shown to be important for water binding. Surprisingly, we found pronounced epidermal protein expression of hBD-2, which may be related to disturbed epidermal differentiation and inflammation. hBD-2 showed a weak, although significant, antifungal activity against T. rubrum in the turbidimetric assay and the immunohistological staining was somewhat less pronounced in areas directly underneath fungal hyphae in the stratum corneum. Together, we describe profound changes in skin barrier structure and function, epidermal proliferation, and differentiation including pronounced protein expression of hBD-2 in tinea corporis.