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Majella E Lane - One of the best experts on this subject based on the ideXlab platform.
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12r lipoxygenase activity is reduced in photodamaged facial stratum corneum a novel activity assay indicates a key function in Corneocyte maturation
International Journal of Cosmetic Science, 2019Co-Authors: D Guneri, Majella E Lane, R Voegeli, M R Munday, A V RawlingsAbstract:BACKGROUND: During the late stage of keratinocyte differentiation Corneocytes gain a strong protein-lipid structure: the Corneocyte envelopes (CE), composed of the inner Corneocyte protein envelope (CPE) and the outer Corneocyte lipid envelope (CLE). The hydrophobicity of CEs depends on the covalent attachment of linoleoyl-acyl-ceramides by transglutaminases (TG). These ceramides are processed by a range of other enzymes, including 12R-lipoxygenase (12R-LOX), before the covalent attachment of the free ω-hydroxyceramides to the CPE surface to form the CLE. The mechanical strength of CE is obtained with the formation of isodipeptide bonds by transglutaminase. The increase in hydrophobicity and rigidity leads to CE maturation which supports the integrity and mechanical resistance of the stratum corneum (SC). OBJECTIVES: The aim of this work was to develop and validate a novel enzyme activity assay for 12R-LOX in tape strippings of photo-exposed (PE) cheek and photo-protected (PP) post auricular SC of healthy Chinese volunteers (n=12; age 25 ± 3 years). RESULTS: A fluorescence based assay was developed with ethyl linoleic acid as the substrate and a polyclonal antibody against 12R-LOX as an inhibitor. The specificity was shown by the lack of effect by a LOX inhibitor (ML351) and an epidermal-type lipoxygenase 3 (eLOX3) antibody on the acquired 12R-LOX activity. Reduced 12R-LOX activity was observed in the outer compared to the inner SC layers. Moreover, dramatically lower activity was shown in the PE vs PP samples. Furthermore, the enzyme activity has a positive correlation (r= 0.94 ± 0.03) with CE maturity, in particular hydrophobicity, and a negative correlation (r= -0.96 ± 0.01) with transepidermal water loss (TEWL). CONCLUSION: This novel enzyme assay revealed a lower 12R-LOX activity in tape strippings from PE cheek for the first time. This finding is in line with less mature CEs and higher TEWL compared to PP post auricular samples. This study indicates a strong link between 12R-LOX activity and CE maturation and SC integrity.
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early life regional and temporal variation in filaggrin derived natural moisturizing factor filaggrin processing enzyme activity Corneocyte phenotypes and plasmin activity implications for atopic dermatitis
British Journal of Dermatology, 2018Co-Authors: Maeve A. Mcaleer, Majella E Lane, Sanja Kezic, Ivone Jakasa, Alan D Irvine, A V Rawlings, R Voegeli, C P F Odonnell, W H I McleanAbstract:Background: Filaggrin is central to the pathogenesis of atopic dermatitis (AD). The cheeks are a common initiation site of infantile AD. Regional and temporal expression of levels of filaggrin degradation products [natural moisturizing factors (NMFs)], activities of filaggrin‐processing enzymes [bleomycin hydrolase (BH) and calpain‐1 (C‐1)] and plasmin, and Corneocyte envelope (CE) maturity in early life are largely unknown. / Objectives: We conducted a cross‐sectional, observational study investigating regional and age‐dependent variations in NMF levels, activity of proteases and CE maturity in stratum corneum (SC) from infants to determine whether these factors could explain the observed predilection sites for AD in early life. / Methods: We measured NMF using a tape‐stripping method at seven sites in the SC of 129 children (aged < 12 months to 72 months) and in three sites in 56 neonates and infants (< 48 h to 3 months). In 37 of these neonates and infants, Corneocyte size, maturity, BH, C‐1 and plasmin activities were determined. / Results: NMF levels are low at birth and increase with age. Cheek SC, compared with elbow flexure and nasal tip, has the lowest NMF in the first year of life and is the slowest to reach stable levels. Cheek Corneocytes remain immature. Plasmin, BH and C‐1 activities are all elevated by 1 month of age in exposed cheek skin, but not in elbow skin. / Conclusions: Regional and temporal differences in NMF levels, CE maturity and protease activities may explain the predilection for AD to affect the cheeks initially and are supportive of this site as key for allergen priming in early childhood. These observations will help design early intervention and treatment strategies for AD.
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variation in the activities of late stage filaggrin processing enzymes calpain 1 and bleomycin hydrolase together with pyrrolidone carboxylic acid levels Corneocyte phenotypes and plasmin activities in non sun exposed and sun exposed facial stratum c
International Journal of Cosmetic Science, 2016Co-Authors: R Voegeli, A V Rawlings, B Summers, M R Munday, Majella E LaneAbstract:BACKGROUND: Knowledge of the ethnic differences and effects of photodamage on the relative amounts of natural moisturizing factor (NMF) together with filaggrin processing enzymes in facial stratum corneum is limited. Our aim was to characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and to relate them to plasmin activities and Corneocyte maturation. METHODS: Enzyme activities, PCA levels and Corneocyte maturation were determined from facial tape strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects living in South Africa. RESULTS: PCA concentration levels were of the order AA > BA > C subjects, and the highest activities of BH were present in the AA subjects. BH activities were greater on the photoexposed sites for the BA and C subjects, but they were only numerically elevated in the AA subjects. Photoprotected sites had an increase in C-1 activity in pigmented groups (C and BA), whereas in the AA subjects, the opposite was measured. Plasmin activities were greater on the cheek compared with the PA site for the AA and C subjects, but the activity was low in the BA subjects. In both test sites, the AA, but not the BA and C subjects, had smaller, parakeratotic and less mature Corneocytes. CONCLUSION: Variation in PCA levels has been found for different ethnic groups in this study (AA > BA > C subjects). The values in the AA subjects are surprising as one might expect that the lack of pigmentation, and thereby increased photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was observed in the AA subjects indicating that BH is associated with PCA production to a greater extent. Surprisingly, Corneocyte maturation is still impaired with elevated PCA levels in AA subjects. The higher levels of plasmin and BH activities on the cheeks, especially for AA and C subjects, suggest that they can be used as markers for epidermal photodamage.
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influence of aqueous cream bp on Corneocyte size maturity skin protease activity protein content and transepidermal water loss
British Journal of Dermatology, 2011Co-Authors: D Mohammed, Jonathan Hadgraft, P J Matts, Majella E LaneAbstract:Summary Background Aqueous Cream BP is frequently prescribed for patients with eczema and is known to induce sensitivity in certain patients and also to decrease the thickness of the stratum corneum (SC). We have previously reported methodology to quantify Corneocyte maturity and size, protease activity and protein content within different levels of the SC. Objectives The aim of the present study was to investigate changes in Corneocyte size, Corneocyte maturity, selected protease activities, protein content and transepidermal water loss (TEWL) in normal skin after a 28-day application of Aqueous Cream BP. Methods The left and right mid volar forearms of six healthy female volunteers were selected as the study sites. Aqueous Cream BP was applied twice daily to treated sites for 28 days. At the end of this period, the site was tape-stripped and Corneocyte maturity, Corneocyte size and protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and the inflammatory proteases tryptase and plasmin were measured. Protein content and TEWL measurements were also recorded. Results Corneocyte maturity and size decreased with increasing number of tape strips, and were significantly lower in treated sites compared with untreated sites. Protease activity and TEWL values were higher (P < 0·05) for the treated sites compared with untreated sites. The amount of protein removed from deeper layers of treated sites was significantly lower than from untreated sites. Conclusions We report rapid minimally invasive measures of the effects of Aqueous Cream BP at the cellular and molecular level of the skin. Treatment with this formulation is associated with increased desquamatory and inflammatory protease activity. Changes in Corneocyte maturity and size are also indicative of accelerated skin turnover induced by chronic application of this emollient. These findings question firmly the routine prescription of this preparation as a moisturizer in patients with atopic dermatitis.
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influence of aqueous cream bp on Corneocyte size maturity skin protease activity protein content and transepidermal water loss
British Journal of Dermatology, 2011Co-Authors: D Mohammed, Jonathan Hadgraft, P J Matts, Majella E LaneAbstract:BACKGROUND: Aqueous Cream BP is frequently prescribed for patients with eczema and is known to induce sensitivity in certain patients and also to decrease the thickness of the stratum corneum (SC). We have previously reported methodology to quantify Corneocyte maturity and size, protease activity and protein content within different levels of the SC. OBJECTIVES: The aim of the present study was to investigate changes in Corneocyte size, Corneocyte maturity, selected protease activities, protein content and transepidermal water loss (TEWL) in normal skin after a 28-day application of Aqueous Cream BP. METHODS: The left and right mid volar forearms of six healthy female volunteers were selected as the study sites. Aqueous Cream BP was applied twice daily to treated sites for 28 days. At the end of this period, the site was tape-stripped and Corneocyte maturity, Corneocyte size and protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and the inflammatory proteases tryptase and plasmin were measured. Protein content and TEWL measurements were also recorded. RESULTS: Corneocyte maturity and size decreased with increasing number of tape strips, and were significantly lower in treated sites compared with untreated sites. Protease activity and TEWL values were higher (P < 0·05) for the treated sites compared with untreated sites. The amount of protein removed from deeper layers of treated sites was significantly lower than from untreated sites. CONCLUSIONS: We report rapid minimally invasive measures of the effects of Aqueous Cream BP at the cellular and molecular level of the skin. Treatment with this formulation is associated with increased desquamatory and inflammatory protease activity. Changes in Corneocyte maturity and size are also indicative of accelerated skin turnover induced by chronic application of this emollient. These findings question firmly the routine prescription of this preparation as a moisturizer in patients with atopic dermatitis.
Jonathan Hadgraft - One of the best experts on this subject based on the ideXlab platform.
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influence of aqueous cream bp on Corneocyte size maturity skin protease activity protein content and transepidermal water loss
British Journal of Dermatology, 2011Co-Authors: D Mohammed, Jonathan Hadgraft, P J Matts, Majella E LaneAbstract:Summary Background Aqueous Cream BP is frequently prescribed for patients with eczema and is known to induce sensitivity in certain patients and also to decrease the thickness of the stratum corneum (SC). We have previously reported methodology to quantify Corneocyte maturity and size, protease activity and protein content within different levels of the SC. Objectives The aim of the present study was to investigate changes in Corneocyte size, Corneocyte maturity, selected protease activities, protein content and transepidermal water loss (TEWL) in normal skin after a 28-day application of Aqueous Cream BP. Methods The left and right mid volar forearms of six healthy female volunteers were selected as the study sites. Aqueous Cream BP was applied twice daily to treated sites for 28 days. At the end of this period, the site was tape-stripped and Corneocyte maturity, Corneocyte size and protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and the inflammatory proteases tryptase and plasmin were measured. Protein content and TEWL measurements were also recorded. Results Corneocyte maturity and size decreased with increasing number of tape strips, and were significantly lower in treated sites compared with untreated sites. Protease activity and TEWL values were higher (P < 0·05) for the treated sites compared with untreated sites. The amount of protein removed from deeper layers of treated sites was significantly lower than from untreated sites. Conclusions We report rapid minimally invasive measures of the effects of Aqueous Cream BP at the cellular and molecular level of the skin. Treatment with this formulation is associated with increased desquamatory and inflammatory protease activity. Changes in Corneocyte maturity and size are also indicative of accelerated skin turnover induced by chronic application of this emollient. These findings question firmly the routine prescription of this preparation as a moisturizer in patients with atopic dermatitis.
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influence of aqueous cream bp on Corneocyte size maturity skin protease activity protein content and transepidermal water loss
British Journal of Dermatology, 2011Co-Authors: D Mohammed, Jonathan Hadgraft, P J Matts, Majella E LaneAbstract:BACKGROUND: Aqueous Cream BP is frequently prescribed for patients with eczema and is known to induce sensitivity in certain patients and also to decrease the thickness of the stratum corneum (SC). We have previously reported methodology to quantify Corneocyte maturity and size, protease activity and protein content within different levels of the SC. OBJECTIVES: The aim of the present study was to investigate changes in Corneocyte size, Corneocyte maturity, selected protease activities, protein content and transepidermal water loss (TEWL) in normal skin after a 28-day application of Aqueous Cream BP. METHODS: The left and right mid volar forearms of six healthy female volunteers were selected as the study sites. Aqueous Cream BP was applied twice daily to treated sites for 28 days. At the end of this period, the site was tape-stripped and Corneocyte maturity, Corneocyte size and protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and the inflammatory proteases tryptase and plasmin were measured. Protein content and TEWL measurements were also recorded. RESULTS: Corneocyte maturity and size decreased with increasing number of tape strips, and were significantly lower in treated sites compared with untreated sites. Protease activity and TEWL values were higher (P < 0·05) for the treated sites compared with untreated sites. The amount of protein removed from deeper layers of treated sites was significantly lower than from untreated sites. CONCLUSIONS: We report rapid minimally invasive measures of the effects of Aqueous Cream BP at the cellular and molecular level of the skin. Treatment with this formulation is associated with increased desquamatory and inflammatory protease activity. Changes in Corneocyte maturity and size are also indicative of accelerated skin turnover induced by chronic application of this emollient. These findings question firmly the routine prescription of this preparation as a moisturizer in patients with atopic dermatitis.
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the relationship between transepidermal water loss and skin permeability
International Journal of Pharmaceutics, 2010Co-Authors: Marta Machado, Teresa M Salgado, Jonathan Hadgraft, Majella E LaneAbstract:Transepidermal water loss (TEWL) is a measure of the steady-state water vapour flux crossing the skin to the external environment and it has been used extensively to characterise skin barrier function. We have previously hypothesised that in vivo TEWL is directly related to the reciprocal of the diffusional permeation pathlength through the stratum corneum (SC). The aim of the present paper is to validate experimentally this hypothesis. Ninety volunteers were recruited and TEWL and Corneocyte surface areas were measured for six anatomic sites. The number of cell layers in the SC was calculated for each anatomic site in order to estimate the geometric pathlength for water efflux. Significant anatomic site variability was found for both TEWL and Corneocyte surface area which were inversely correlated. A direct reciprocal relationship between TEWL and pathlength was determined, with TEWL values tending to zero when Corneocytes are infinitely large. In general, skin sites with smaller Corneocytes have fewer cell layers, with shorter permeation pathlengths and higher TEWL values. The results confirm our previous hypothesis and suggest that TEWL may be used to characterise the permeation routes for different anatomic sites.
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transepidermal water loss and skin site a hypothesis
International Journal of Pharmaceutics, 2009Co-Authors: Jonathan Hadgraft, Majella E LaneAbstract:The skin has a unique barrier to the ingress of hazardous materials and the egress of water. The barrier properties of the skin reside in the outer 15 microm, the stratum corneum, which has often been regarded as rather inert or even dead. The excellent barrier properties of this thin layer result from its structure which comprises of pentagonal or hexagonal Corneocytes embedded in a lipid matrix. Corneocyte turnover and epidermal proliferation is controlled by desquamatory proteases and protease inhibitors in the epidermis. Disorders in barrier function and disruption of barrier homeostasis have been associated with changes in the expression patterns of epidermal serine proteases and variations in serine protease activity have also been identified at different body sites. The major route of permeation is around the Corneocytes, therefore, the larger the Corneocytes the longer the route for the permeation. Corneocyte size is dependent on the site on the body and this can be directly related to the permeability. For example, the face has thinner skin and the Corneocyte size is smaller than the arm. This results in a shorter path for a drug to penetrate. Transepidermal water loss (TEWL) is a measure of the amount of water from within the skin to the external atmosphere. Rougier et al. showed that variations in Corneocyte size at different anatomical sites were reflected in TEWL at these sites. The path length at different body sites was calculated using a simple geometric equation and a direct reciprocal relationship between the path length and TEWL was identified. A linear trend between cell size and cell layers at different sites is also evident in the data. Since higher protease activity should result in smaller Corneocyte sizes and fewer cell layers, this in turn may be related to reported variations in enzyme activity at these sites.
Leopold Eckhart - One of the best experts on this subject based on the ideXlab platform.
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filaggrin expression and processing deficiencies impair Corneocyte surface texture and stiffness in mice
Journal of Investigative Dermatology, 2020Co-Authors: Jacob P Thyssen, Ivone Jakasa, Christoph Riethmuller, Michael P Schon, Andrea Braun, M Haftek, Padraic G Fallon, Jacek Wroblewski, Hieronim Jakubowski, Leopold EckhartAbstract:Abundant Corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and Corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp−/−), filaggrin (Flgft/ft and Flg−/−), filaggrin-hornerin (FlgHrnr−/−), and bleomycin hydrolase (Blmh−/−) were investigated. Sasp−/− and Flg−/− were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp−/−. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect Corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and Corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.
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terminal differentiation of nail matrix keratinocytes involves up regulation of dnase1l2 but is independent of caspase 14 expression
Differentiation, 2007Co-Authors: Karin Jager, Heinz Fischer, Erwin Tschachler, Leopold EckhartAbstract:Terminal differentiation of keratinocytes in the epidermis and in epidermal appendages results in specialized forms of cell death. Keratinocytes of the nail matrix differentiate into nail Corneocytes, the building blocks of the nail plate. Here, we show that, in contrast to the abrupt breakdown of the nucleus during Corneocyte formation of epidermal keratinocytes, chromatin undergoes progressive condensation over several nail matrix cell layers below the transition zone to the nail plate, where nuclear DNA disappears. Virtually all keratinocytes in the cell layer immediately beneath the nail plate contained terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling-positive DNA fragments. Nail matrix keratinocytes lacked processed caspase-3, a marker of apoptosis, and did not express caspase-14, a protease up-regulated during terminal differentiation of epidermal keratinocytes. By contrast, DNase1L2, which is also up-regulated during the differentiation of epidermal keratinocytes and plays an essential role in differentiation-associated degradation of nuclear DNA in epidermal keratinocytes, was strongly expressed in the nail matrix–nail plate transition layer. Our results show that caspase-14 is not strictly, if at all, required for differentiation-associated keratinocyte cell death and implicates DNase1L2 in terminal differentiation of nail matrix keratinocytes.
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Terminal differentiation of nail matrix keratinocytes involves up‐regulation of DNase1L2 but is independent of caspase‐14 expression
Differentiation, 2007Co-Authors: Karin Jager, Heinz Fischer, Erwin Tschachler, Leopold EckhartAbstract:Terminal differentiation of keratinocytes in the epidermis and in epidermal appendages results in specialized forms of cell death. Keratinocytes of the nail matrix differentiate into nail Corneocytes, the building blocks of the nail plate. Here, we show that, in contrast to the abrupt breakdown of the nucleus during Corneocyte formation of epidermal keratinocytes, chromatin undergoes progressive condensation over several nail matrix cell layers below the transition zone to the nail plate, where nuclear DNA disappears. Virtually all keratinocytes in the cell layer immediately beneath the nail plate contained terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling-positive DNA fragments. Nail matrix keratinocytes lacked processed caspase-3, a marker of apoptosis, and did not express caspase-14, a protease up-regulated during terminal differentiation of epidermal keratinocytes. By contrast, DNase1L2, which is also up-regulated during the differentiation of epidermal keratinocytes and plays an essential role in differentiation-associated degradation of nuclear DNA in epidermal keratinocytes, was strongly expressed in the nail matrix–nail plate transition layer. Our results show that caspase-14 is not strictly, if at all, required for differentiation-associated keratinocyte cell death and implicates DNase1L2 in terminal differentiation of nail matrix keratinocytes.
Christoph Riethmuller - One of the best experts on this subject based on the ideXlab platform.
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filaggrin expression and processing deficiencies impair Corneocyte surface texture and stiffness in mice
Journal of Investigative Dermatology, 2020Co-Authors: Jacob P Thyssen, Ivone Jakasa, Christoph Riethmuller, Michael P Schon, Andrea Braun, M Haftek, Padraic G Fallon, Jacek Wroblewski, Hieronim Jakubowski, Leopold EckhartAbstract:Abundant Corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and Corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp−/−), filaggrin (Flgft/ft and Flg−/−), filaggrin-hornerin (FlgHrnr−/−), and bleomycin hydrolase (Blmh−/−) were investigated. Sasp−/− and Flg−/− were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp−/−. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect Corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and Corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.
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actinic keratosis and surrounding skin exhibit changes in Corneocyte surface topography and decreased levels of filaggrin degradation products
Experimental Dermatology, 2020Co-Authors: Anne J Keurentjes, Sanja Kezic, Ivone Jakasa, Kornelis D De Witt, Lars Ruther, Patrick M J H Kemperman, Christoph RiethmullerAbstract:: Actinic keratosis (AK) is a frequent pre-malignant skin lesion mainly caused by chronic sun exposure. AK lesions are often surrounded by invisible, subclinical alterations, called field of cancerization (FoC). Definition of FoC is of importance for therapy management, however the criteria and non-invasive tools to characterize FoC are lacking. Atomic force microscopy (AFM) proved to be a suitable tool for detection of changes in the Corneocyte surface topography in inflammatory skin diseases, which share similar clinical features with AK such as hyper- and parakeratosis. Therefore, in this study we applied AFM to investigate AK and surrounding skin obtained by non-invasive collection of the stratum corneum (SC) with adhesive tapes. Furthermore, we determined degradation products of structural protein filaggrin (natural moisturizing factor, NMF), which previously showed association with the changes in Corneocyte surface topography. Ten patients with multiple AK on the face were recruited from the outpatient clinic. SC samples were collected from the AK lesion, skin sites adjacent to the AK, 5 cm from the AK, and retroauricular area. Corneocyte surface topography was determined by AFM, and NMF by liquid chromatography. The AK lesion showed alterations of the Corneocyte surface topography characterized by an increased number of nano-size protrusions, which gradually decreased with the distance from the lesion. NMF levels show an inverse pattern. Atomic force microscopy showed to be a suitable tool to detect changes in the Corneocyte surface topography on the AK lesion and surrounding skin in a non-invasive manner.
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concentration of filaggrin monomers its metabolites and Corneocyte surface texture in individuals with a history of atopic dermatitis and controls
Journal of The European Academy of Dermatology and Venereology, 2018Co-Authors: Sanja Kezic, Christoph Riethmuller, K A Engebretsen, Josefine Bandier, Niels H H Heegaard, Berit C Carlsen, Allan LinnebergAbstract:Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Notably, a high number of nano-scale protrusions on the surface of Corneocytes, which can be expressed by the Dermal Texture Index (DTI), was recently associated with pediatric AD, loss-of-function mutations in filaggrin gene (FLG), and reduced levels of natural moisturizing factors (NMF). No study has so far examined the association between these parameters and monomeric filaggrin levels in adults. To determine DTI, monomeric filaggrin and NMF in healthy controls and a group of patients with controlled dermatitis. A total of 67 adults (20 healthy controls and 47 dermatitis patients) were included. In the patient population, a personal history of AD was diagnosed by the U.K. Working Party's Diagnostic Criteria. All participants were tested for FLG mutations (R501X, 2282del4, R2447X). Transepidermal water loss, monomeric filaggrin, DTI and NMF were measured. In the patient population, 78.7% (37/47) had a history of AD and 59.5% (28/47) had FLG mutations. Patients had significantly higher levels of DTI and significantly lower levels of monomeric filaggrin and NMF compared to the 20 healthy controls. Among patients, reduced level of monomeric filaggrin and NMF correlated with the presence of FLG mutations and clinical phenotypes such as xerosis, palmar hyperlinearity and AD. Among healthy controls, DTI was significantly higher in the oldest age group compared to the two younger age groups. A significant difference in DTI, monomeric filaggrin and NMF levels was found when comparing dermatitis patients with healthy controls. These findings suggest that even mild dermatitis or non-visible inflammation has a significant and negative effect on the skin barrier as inflammation is known to reduce filaggrin levels. DTI was significantly increased in aged individuals in the healthy control group, suggesting a gradual change in Corneocyte morphology with age. This article is protected by copyright. All rights reserved
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effect of allergens and irritants on levels of natural moisturizing factor and Corneocyte morphology
Contact Dermatitis, 2017Co-Authors: Ivone Jakasa, Christoph Riethmuller, Sjors A Koppes, Suzana Ljubojevic Hadžavdic, Nika Franceschi, Ružica Jurakic Toncic, Branka Marinovic, A V Rawlings, R VoegeliAbstract:SummaryBackground The irritant sodium lauryl sulfate (SLS) is known to cause a decrease in the stratum corneum level of natural moisturizing factor (NMF), which in itself is associated with changes in Corneocyte surface topography. Objective To explore this phenomenon in allergic contact dermatitis. Methods Patch testing was performed on patients with previously positive patch test reactions to potassium dichromate (Cr), nickel sulfate (Ni), methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI), or p-phenylenediamine. Moreover, a control (pet.) patch and an irritant (SLS) patch were applied. After 3 days, the stratum corneum from tested sites was collected, and NMF levels and Corneocyte morphology, expressed as the amount of circular nanosize objects, quantified according to the Dermal Texture Index (DTI), were determined. Results Among allergens, only MCI/MI reduced NMF levels significantly, as did SLS. Furthermore, only MCI/MI caused remarkable changes at the microscopic level; the Corneocytes were hexagonal-shaped with pronounced cell borders and a smoother surface. The DTI was increased after SLS exposure but not after allergen exposure. Conclusions MCI/MI significantly decreased NMF levels, similarly to SLS. The altered Corneocyte morphology suggests that skin barrier damage plays a role in the pathogenesis of MCI/MI contact allergy. The DTI seems to differentiate reactions to SLS from those to the allergens tested, as SLS was the only agent that caused a DTI increase.
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filaggrin breakdown products determine Corneocyte conformation in patients with atopic dermatitis
The Journal of Allergy and Clinical Immunology, 2015Co-Authors: Christoph Riethmuller, Maeve A. Mcaleer, Jonas Franz, Sjors A Koppes, Rawad Abdayem, Marek Haftek, Linda E Campbell, Stephanie F Maccallum, W Irwin H Mclean, Alan D IrvineAbstract:Background: Loss-of-function (LOF) mutations in the filaggrin gene (FLG) are a well-replicated risk factor for atopic dermatitis (AD) and are known to cause an epidermal barrier defect. The nature of this barrier defect is not fully understood. Patients with AD with FLG LOF mutations are known to have more persistent disease, more severe disease, and greater risk of food allergies and eczema herpeticum. Abnormalities in Corneocyte morphology have been observed in patients with AD, including prominent villus-like projections (VP); however, these ultrastructural features have not been systematically studied in patients with AD in relation to FLG genotype and acute and convalescent status. Objective: We sought to quantitatively explore the relationship between FLG genotype, filaggrin breakdown products (natural moisturizing factor [NMF]), and Corneocyte morphology in patients with AD. Methods: We studied 15 children at first presentation of AD and after 6 weeks of standard therapy. We applied atomic force microscopy to study Corneocyte conformation in patients with AD stratified by FLG status and NMF level. By using a new quantitative methodology, the number of VPs per investigated Corneocyte area was assessed and expressed as the Dermal Texture Index score. Corneocytes were also labeled with an anticorneodesmosin antibody and visualized with scanning electron microscopy. Results: We found a strong correlation between NMF levels and Dermal Texture Index scores in both acute and convalescent states (respective r 52 0.80 and 20.75, P < .001 and P 5 .002). Most, but not all, VPs showed the presence of corneodesmosin abundantly all over the cell surface in homozygous/compound heterozygous FLG patients and, to a lesser extent, in heterozygous and wild-type patients. Conclusions: NMF levels are highly correlated with Corneocyte morphology in patients with AD. These Corneocyte conformational changes shed further insight into the filaggrindeficient phenotype and help explain the barrier defect in patients with AD with FLG LOF mutations. (J Allergy Clin Immunol 2015;nnn:nnn-nnn.)
D Mohammed - One of the best experts on this subject based on the ideXlab platform.
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influence of aqueous cream bp on Corneocyte size maturity skin protease activity protein content and transepidermal water loss
British Journal of Dermatology, 2011Co-Authors: D Mohammed, Jonathan Hadgraft, P J Matts, Majella E LaneAbstract:Summary Background Aqueous Cream BP is frequently prescribed for patients with eczema and is known to induce sensitivity in certain patients and also to decrease the thickness of the stratum corneum (SC). We have previously reported methodology to quantify Corneocyte maturity and size, protease activity and protein content within different levels of the SC. Objectives The aim of the present study was to investigate changes in Corneocyte size, Corneocyte maturity, selected protease activities, protein content and transepidermal water loss (TEWL) in normal skin after a 28-day application of Aqueous Cream BP. Methods The left and right mid volar forearms of six healthy female volunteers were selected as the study sites. Aqueous Cream BP was applied twice daily to treated sites for 28 days. At the end of this period, the site was tape-stripped and Corneocyte maturity, Corneocyte size and protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and the inflammatory proteases tryptase and plasmin were measured. Protein content and TEWL measurements were also recorded. Results Corneocyte maturity and size decreased with increasing number of tape strips, and were significantly lower in treated sites compared with untreated sites. Protease activity and TEWL values were higher (P < 0·05) for the treated sites compared with untreated sites. The amount of protein removed from deeper layers of treated sites was significantly lower than from untreated sites. Conclusions We report rapid minimally invasive measures of the effects of Aqueous Cream BP at the cellular and molecular level of the skin. Treatment with this formulation is associated with increased desquamatory and inflammatory protease activity. Changes in Corneocyte maturity and size are also indicative of accelerated skin turnover induced by chronic application of this emollient. These findings question firmly the routine prescription of this preparation as a moisturizer in patients with atopic dermatitis.
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influence of aqueous cream bp on Corneocyte size maturity skin protease activity protein content and transepidermal water loss
British Journal of Dermatology, 2011Co-Authors: D Mohammed, Jonathan Hadgraft, P J Matts, Majella E LaneAbstract:BACKGROUND: Aqueous Cream BP is frequently prescribed for patients with eczema and is known to induce sensitivity in certain patients and also to decrease the thickness of the stratum corneum (SC). We have previously reported methodology to quantify Corneocyte maturity and size, protease activity and protein content within different levels of the SC. OBJECTIVES: The aim of the present study was to investigate changes in Corneocyte size, Corneocyte maturity, selected protease activities, protein content and transepidermal water loss (TEWL) in normal skin after a 28-day application of Aqueous Cream BP. METHODS: The left and right mid volar forearms of six healthy female volunteers were selected as the study sites. Aqueous Cream BP was applied twice daily to treated sites for 28 days. At the end of this period, the site was tape-stripped and Corneocyte maturity, Corneocyte size and protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and the inflammatory proteases tryptase and plasmin were measured. Protein content and TEWL measurements were also recorded. RESULTS: Corneocyte maturity and size decreased with increasing number of tape strips, and were significantly lower in treated sites compared with untreated sites. Protease activity and TEWL values were higher (P < 0·05) for the treated sites compared with untreated sites. The amount of protein removed from deeper layers of treated sites was significantly lower than from untreated sites. CONCLUSIONS: We report rapid minimally invasive measures of the effects of Aqueous Cream BP at the cellular and molecular level of the skin. Treatment with this formulation is associated with increased desquamatory and inflammatory protease activity. Changes in Corneocyte maturity and size are also indicative of accelerated skin turnover induced by chronic application of this emollient. These findings question firmly the routine prescription of this preparation as a moisturizer in patients with atopic dermatitis.