Ehrhardt Proksch

Kiel University | CAU · Department of Dermatology, Venereology and Allergology

Die Permeabilitätsbarriere spielt bei zahlreichen Hauterkrankungen eine Rolle. Besonders gut aufgeklärt ist die Bedeutung der Barriere bei ekzematösen Erkrankungen. Bei einem irritativ-toxischen Kontaktekzem ist die Störung der Permeabilitätsbarriere durch irritativ-toxische Noxen der erste Schritt in der Pathogenese. Nur nach Schädigung der Barrie...

The aim of the study was to investigate the expression of Toll-like receptor (TLR) 2 and 4 on keratinocytes in atopic dermatitis, contact dermatitis, and psoriasis by PCR and by immunohistochemistry including confocal microscopy. Confocal microscopy revealed a granular intracellular expression pattern for TLR 2 and a homogenous intracellular expres...

Atopic dermatitis is the result of complex interactions between environmental and genetic factors influencing the epidermal structure and function, as well as the immune system. Epidermal changes, including the defective epidermal permeability barrier, have recently been intensively investigated recently and seem to be a hallmark of disease pathoge...

The proteolytic regulation of the desquamation process by kallikrein-related peptidases (KLKs) is crucial for epidermal barrier function, and elevated KLK levels have been reported in atopic dermatitis. KLKs are controlled by specific inhibitors of the serine protease inhibitor of Kazal-type (Spink) family. Recently, SPINK6 was shown to be present...

In superficial tinea and pityriasis versicolor, the causative fungi are for the most part confined to the stratum corneum which is barely reached by leukocytes. Therefore, a role of non-cellular components in the epidermal antifungal defence was suggested. To investigate the presence of such factors in these infections, the expression of human beta...

Patients with atopic dermatitis (AD) have an epidermal barrier dysfunction, which allows invasion of allergens to occur. Stratum corneum skin barrier is formed by corneocytes and extracellular lipids extruded from the epidermal lamellar bodies. In a controlled, randomized, double-blinded, right-left comparison study we investigated the effect of pi...

A crucial role of the epidermal permeability barrier is obvious in contact dermatitis. An intact skin barrier prevents the penetration of harmful substances into the skin. Irritants and allergens that stay on the skin surface and come into contact with the stratum corneum only do not harm the skin. After disruption of the skin barrier, however, irr...

The S100 fused-type proteins (SFTPs) are thought to be involved in the barrier formation and function of the skin. Mutations in the profilaggrin gene, one of the best investigated members of this family, are known to be the major risk factors for ichthyosis vulgaris and atopic dermatitis. Recently, we identified human filaggrin-2 as a new member of...

Induction of DNA damage by UVR is the key event in photocarcinogenesis. IL-12 and IL-23 are related heterodimeric cytokines consisting of a common p40 unit and a p35/IL-12 and a p19/IL-23 chain, respectively. Both exert immunomodulatory activities but are also found to reduce UVR-induced DNA damage presumably via induction of DNA repair. As both cy...

β-Defensins are antimicrobial peptides of the innate immune system produced in the skin by various stimuli, including proinflammatory cytokines, bacterial infection, and exposure to UV radiation (UVR). In this study we demonstrate that the UVR-inducible antimicrobial peptide murine β-defensin-14 (mBD-14) switches CD4(+)CD25(-) T cells into a regula...

Topical corticosteroids and calcineurin inhibitors are well-known treatments of atopic dermatitis (AD) but differ in their efficacy and side effects. We recently showed that betamethasone valerate (BM) although clinically more efficient impaired skin barrier repair in contrast to pimecrolimus in AD. This study elucidates the mode of action of topic...

Die Windeldermatitis zählt zu den häufigsten Hauterkrankungen im Säuglings- und Kleinkindesalter. Sie ist als irritatives Kontaktekzem aufzufassen, wobei im Wesentlichen komplexe Interaktionen von Urin und Stuhl, okklusive Bedingungen mit Hyperhydratation des Stratum corneum sowie Druck und Reibung durch die Windel ursächlich sind. Dieses sind best...

Diaper dermatitis is one of the most common skin diseases during infancy and childhood. It is a type of irritant contact eczema resulting from a complex interaction between urine and feces under occlusive conditions in combination with the hyperhydration of the stratum corneum, pressure and friction under the diaper. These conditions pave the way f...

An intact skin barrier prevents the penetration of harmful substances from the environment into the skin and prevents occupational skin diseases. In contact dermatitis, the first step in pathology is the disruption of the skin barrier. The skin barrier often gets disrupted by chronic exposure to water plus detergents or solvents. Thereafter, irrita...

It has been suggested that the increased rate of bacterial infection in atopic dermatitis (AD) may be caused by reduced antimicrobial protein (AMP) expression. We were interested whether common treatments in AD affect antimicrobial defense. We investigated the effects of topically applied corticosteroids betamethasone valerate (BV) and triamacinolo...

A side effect of radiotherapy for breast cancer is acute radiodermatitis. It is a common practice to keep irradiated skin dry on account of data from the 1950s that suggested this regimen limits dermatitis. However, severe dryness of the skin induced by irradiation results in itching and discomfort. Dry skin is characterized by scaliness, epidermal...

There is increasing concern about the interaction between infrared radiation (IR) and ultraviolet radiation (UVR) with regard to carcinogenesis because prolonged solar exposure is associated with an increased cumulative load not only of UVR but also of IR. We recently demonstrated that IR-pretreatment reduces UVR-induced apoptosis. As this might su...

c-Jun N-terminal kinases (JNKs, also called stress activated protein kinases) and the extra-cellular signal responsive kinases (ERKs) exert different functions in mitogenesis, maturation and differentiation of immune and epithelial cells. We investigated specific functions of individual JNK and ERK isoforms in skin permeability barrier repair and i...

Protection of the skin against microbiological infection is provided by the permeability barrier and by antimicrobial proteins. We asked whether the expression of murine β-defensins (mBDs)-1, -3, and -14-orthologs of human β-defensins hBD-1, -2, and -3, respectively--is stimulated by mechanically/physicochemically (tape stripping or acetone treatme...

Human skin can defend itself against potentially invading microorganisms by production of antimicrobial peptides (AMPs). The expression of AMPs in atopic dermatitis (AD) is still emerging. To gain more insight into the role of AMPs in AD, we systematically analyzed the expression of ribonuclease 7 (RNase 7), psoriasin, and human beta-defensins (hBD...

During the progression of cutaneous melanomas, matrix metalloproteinases (MMPs) facilitate the tumour cells to traverse the basement membrane and invade the dermis. In this study, we analysed the expression of MMP19 in the course of melanoma progression. Although MMP19 was absent in melanocytes and melanoma cells of early stages of melanoma develop...

The skin provides an effective barrier between the organism and the environment, preventing the 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, as well as how barrier function is regulated...

Genetic defects leading to skin barrier dysfunction were recognized as risk factors for atopic dermatitis (AD). It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens. We investigated the effect of 2 common treatments, a calcineurin inhibitor and a corticoste...

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...

Allergies to latex or 'rubber chemicals' in medical or other occupationally used gloves are not uncommon. In contrast, very few articles have reported on latex allergy (type I) or allergic contact sensitization to additives (type IV) associated with household gloves, in spite of some 44 million pairs sold in Germany in, e.g., 2006. We seek to deter...

Facial skin is unique in that it gets far more exposure to the external environment than skin on other areas of the body and paradoxically, because it contains the thinnest epidermis and stratum corneum, especially on the eye lid. Environmental attacks contribute to drying of facial skin and damage to the stratum corneum. In recent years, there has...

Please cite this paper as: The skin: an indispensable barrier. Experimental Dermatology 2008.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 overvi...

The innate defense of the skin against microbial threats is influenced by antimicrobial proteins (AMP). Staphylococcus aureus often colonizes the skin of patients with atopic dermatitis (AD). This was explained by diminished expression of AMP including cathelicidin/LL-37, human beta-defensins-2 and -3, and dermcidin. The S100-protein psoriasin is a...

Acute eczema is an inflammatory skin disease characterized by the formation of small intraepidermal blisters, reduction of the adhesion molecule E-cadherin from the keratinocyte surface, and impaired keratinocyte cohesion. Here, we reveal that the disintegrin and metalloprotease ADAM10 is critically involved in regulating E-cadherin cell-surface ex...

Searching the database for mouse homologs of the antimicrobial peptide human beta-defensin-3 (hBD-3) revealed highest identity (69%) to mouse beta-defensin-14 (mBD-14). Recombinant mBD-14 exhibited broad-spectrum, nanomolar microbicidal activity. Treatment of keratinocytes with gamma interferon or transforming growth factor alpha increased mBD-14 g...

Dry skin is a common skin condition as well as a key aspect of a number of diseases such as atopic dermatitis and psoriasis but also of other diseases and systemic conditions. Dry skin has an impact on the patient in terms of discomfort, pruritus and impaired quality of life. Within the overall treatment regimen for these diseases, the use of emoll...

A defect in barrier function is present in atopic dermatitis, potentially playing the causative role in the development of atopic lesions by enabling the penetration of type I environmental allergens into the skin, which consequently initiates immunological reactions and inflammation. This defect may be caused by genetic defects associated with the...

First-degree burns are the most common type of burn, but are often inadequately treated. The methods of treatment and the course of healing are poorly documented owing to the fact that first-degree burns are generally not considered to be a serious injury. First-degree burns can be caused by thermal injury or UV irradiation (sunburn). The pathophys...

First-degree burns are the most common type of burn, but are often inadequately treated. The methods of treatment and the course of healing are poorly documented owing to the fact that first-degree burns are generally not considered to be a serious injury. First-degree burns can be caused by thermal injury or UV irradiation (sunburn). The pathophys...

The CXC-chemokine ligand 16 (CXCL16) is expressed as a transmembrane adhesion molecule and can be released as a chemoattractant. Both functions are carried out by binding of CXCL16 to its receptor, CXC-chemokine receptor 6 (CXCR6). We here provide early evidence that CXCL16 is expressed in situ by epidermal keratinocytes of normal skin on messenger...

Tinea corporis is a superficial mycotic infection resulting in substantial epidermal changes. We determined skin barrier function, epidermal differentiation, and human-β-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 significa...

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 fu...

The sebaceous nevus syndrome describes the rare association of a sebaceous nevus with systemic features such as mental retardation, seizures and colobomas (among others). It is thought to be a cutaneous mosaic inherited as a paradominant trait. Three cases are provided illustrating the intraoral manifestations of the syndrome. The first histologica...

The repair of the permeability barrier to prevent the entry of harmful substances into the body is a goal in wound healing. Semi-occlusive foils, which provide an artificial barrier, are commonly used for the treatment of wounds. We examined the effects of foils on wound contraction, cell migration, and reepithelization. Full-thickness skin wounds...

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 c...

In aged skin, decreased levels of stratum corneum ceramides have been described. Epidermal ceramides are generated by sphingomyelin hydrolysis or synthesis from sphingosin and fatty acids and are degraded by ceramidase. We recently showed that epidermal acid sphingomyelinase (A-SMase) generates ceramides with structural function in the stratum corn...

In this study we analyzed the proteolytic activity of MMP-19 and its impact on keratinocyte migration. In the HaCaT keratinocyte cell line overexpressing wild-type MMP-19 (HaCaT-WT), transmigration through fibrin and type IV collagen matrices was significantly increased compared to cells harboring a catalytically inactive mutant (HaCaT-EA). Studyin...

Magnesium salts, the prevalent minerals in Dead Sea water, are known to exhibit favorable effects in inflammatory diseases. We examined the efficacy of bathing atopic subjects in a salt rich in magnesium chloride from deep layers of the Dead Sea (Mavena(R) Dermaline Mg(46) Dead Sea salt, Mavena AG, Belp, Switzerland). Volunteers with atopic dry ski...

Defensins are broad-spectrum antimicrobial peptides that are components of innate immunity. To date, only epithelial surfaces and blood cells have been shown to produce these cationic peptides in bactericidal concentrations when challenged with microorganisms or inflammatory cytokines. Infections caused by gram-negative pathogens occur only infrequ...

Interleukin-6 (IL-6) is involved in the growth and differentiation of numerous cell types. In the skin it is produced primarily by keratinocytes. The transcription factor STAT3 is activated by cytokines of the IL-6 family. In this study, we examined the involvement of IL-6, soluble IL-6-receptor, and STAT3 in epidermal barrier repair after injury t...

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 an...

We previously demonstrated that the aspartate protease cathepsin D is activated by ceramide derived from acid sphingomyelinase. Increased expression of cathepsin D in the skin has been reported in wound healing, psoriasis and skin tumors. We explored specific functions of cathepsin D during epidermal differentiation. Protein expression and enzymati...

Human keratinocytes are known to express the protease-activated receptors, PAR-1 and PAR-2. Activation of PAR-1 results in increased proliferation, whereas PAR-2 activation results in decreased keratinocyte proliferation. Trypsin activates PAR-1 and in higher concentrations, PAR-2. The aim of this study was to evaluate the overall effect of trypsin...

Most of the matrix metalloproteinases (MMP) are not expressed in normal intact skin but they are upregulated in inflamed or diseased skin. The recently cloned MMP-19 is one of the few MMP members that are also expressed in healthy epidermis. In this study, we found that MMP-19 is generally coexpressed with cytokeratin 14 that is confined to keratin...

Dexpanthenol-containing creams have been widely used for treatment of lesions (superficial wounds) of the skin and mucous membranes. Dexpanthenol is converted in tissues to pantothenic acid, a component of coenzyme A. Coenzyme A catalyses early steps in the synthesis of fatty acids and sphingolipids which are of crucial importance for stratum corne...

Neutrophil infiltration and epidermal hyperproliferation are major histopathologic changes observed in psoriasis. Neutrophils contain human leukocyte elastase, which is thought to be released during neutrophil infiltration of the epidermis. As active human leukocyte elastase is known to be present in psoriatic lesions we were interested whether hum...

Volatile N-nitrosamines have been found in rubber products including gloves, balloons, toys, baby bottle teats, soothers, and condoms. N-Nitrosamines are potent carcinogens, and therefore, European legislation has limited the release of N-nitrosamines and N-nitrosatable compounds in teats and soothers to 0.01-0.1 mg/kg rubber, respectively. Previou...

Point mutations in the suprabasal cytokeratins 1 (K1) or 10 (K10) in humans have been shown to be the cause of the congenital ichthyosis epidermolytic hyperkeratosis. Recently, a K10 deficient mouse model was established serving as a model for epidermolytic hyperkeratosis. Homozygotes suffered from severe skin fragility and died shortly after birth...

The stratum corneum requires ceramides, cholesterol, and fatty acids to provide the cutaneous permeability barrier. The lipids are organized in intercellular membranes exhibiting short- and long-periodicity lamellar phases. In recent years, the phase behavior of barrier lipid mixtures has been studied in vitro. The relationship of human stratum cor...

Wearing of patch test chambers for 1-2 days is uncomfortable for patients. Allergen application by iontophoresis avoids this, but it is unknown so far whether iontophoresis itself interferes with the delayed immune response. We compared the effects occurring 48 h after iontophoresis with distilled water, 0.9% NaCl, and 0.01 M NiSO4 in normal volunt...

Epidermal TNF expression increases in response to cutaneous permeability barrier disruption and wound healing. TNF signaling is mediated by acid and neutral sphingomyelinases (A- and N-SMase), which generate ceramide, an important regulator of proliferation, differentiation, and apoptosis. In the epidermis, ceramide is known to be an integral part...

The WD-40 repeat protein FAN binds to a distinct domain of the p55 receptor for tumor necrosis factor (TNF) and signals the activation of neutral sphingomyelinase (N-SMase). To analyze the physiological role of FAN in vivo, we generated FAN-deficient mice by targeted gene disruption. Mice lacking a functional FAN protein do not show any overt pheno...

In previous studies we have shown that experimental permeability barrier disruption leads to an increase in epidermal lipid and DNA synthesis. Here we investigate whether barrier disruption also influences keratins and cornified envelope proteins as major structural keratinocyte proteins. Cutaneous barrier disruption was achieved in hairless mouse...

The hallmarks of dry skin (xerosis) are scaliness and loss of elasticity. Decreased hydration and a disturbed lipid content of the stratum corneum are also well-known features. The frequency of dry skin increases with ageing. The aim of this study was to examine if these known features of dry skin are related to changes in epidermal proliferation a...