Epidermal Barrier Homeostasis Research Articles

Steroid-sparing effect of emollients in atopic dermatitis and psoriasis

The aim of the present article is to analyze the role of emollients in the topical management of atopic dermatitis and psoriasis and also to review the clinical studies available on the beneficial effect of co-therapy of emollients and topical corticosteroids. Understanding the stratum corneum's key involvement in the pathophysiology of atopic dermatitis and psoriasis has led to the development of new therapeutic approaches for treating not just inflammation but also restoring a healthy skin barrier. While topical corticosteroids are the cornerstones of treatment for atopic dermatitis and psoriasis, the potential risks of overuse (including atrophy, striae, dyspigmentation, and loss in epidermal barrier homeostasis) must be weighed against the benefits. These risks futher increase the necessity of finding non-steroidal treatments. Emollients aid the epidermal barrier function as they improve the oil and lipid levels and restore its protective function. Used regularly, emollients may reduce flare-ups and may also have a direct anti-inflammatory effect and may reduce the need to use topical corticosteroids, i.e. they have a ‘steroid sparing effect’.

774 Receptor tyrosine kinase EPHA2 is required for epidermal barrier homeostasis

774 Receptor tyrosine kinase EPHA2 is required for epidermal barrier homeostasis

Obesity and the microbiome in atopic dermatitis: Therapeutic implications for PPAR-γ agonists

Atopic dermatitis (AD) is an inflammatory skin disease characterized by epidermal barrier disruption, Th2 immune responses to skin allergens and microbial dysbiosis within affected lesions. Studies within the past decade have revealed genetic and environmental factors contributing to AD in children. Obesity is a metabolic disorder that often manifests early in life and is associated with reduced bacterial diversity, leading to skin colonization with lipophilic bacteria and intestinal colonization with pro-inflammatory species. These changes impair epithelial barriers and promote Th17 responses, which may worsen the severity of AD symptoms. While few studies have examined the contribution of microbiota in obesity-induced allergies, there is emerging evidence that PPAR-γ may be an effective therapeutic target. This review discusses the microbiome in pediatric AD, treatment with probiotics, how disease is altered by obesity and potential therapeutic effects of PPAR-γ agonists. While healthy skin contains diverse species adapted for specific niches, lesional skin is highly colonized with Staphylococcus aureus which perpetuates the inflammatory reaction. Treatments for AD should help to restore microbial diversity in the skin and intestine, as well as epithelial barrier function. Pre-clinical models have shown that PPAR-γ agonists can suppress Th17 responses, IgE production and mast cell function, while improving the epidermal barrier and microbial homeostasis. Overall, PPAR-γ agonists may be effective in a subset of patients with AD, and future studies should distinguish their metabolic and anti-inflammatory effects in order to inform the best therapies.

Skin Barrier Function and Its Relationship With IL-17, IL-33, and Filaggrin in Malar Melasma.

The pathogenesis of melasma remains unclear. Interleukin (IL)-17, a proinflammatory mediator, disturbs barrier function. Filaggrin (FLG) is a protein involved in epidermal barrier homeostasis and may be affected by IL-17 and IL-33. To evaluate epidermal barrier function in malar melasma and its association with the expression of FLG, IL-17, and IL-33. Twenty patients with malar melasma were included in this study. Colorimetric and transepidermal water loss (TEWL) was measured in lesional and adjacent unaffected skin at baseline and 30 minutes after barrier disruption using the tape-stripping test. Biopsies from melasma and perilesional skin were performed to evaluate the presence of FLG by immunohistochemistry, and profilaggrin, IL-17, and IL-33 expression were analyzed by reverse transcription-qualitative polymerase chain reaction. After the stripping test, the erythema and TEWL values were higher in the melasma than in the unaffected skin ( P = 0.01). Thirty minutes later, TEWL diminished, but it remained higher than in the perilesional skin. Profilaggrin increased as TEWL gradually decreased (R = -0.68, P = 0.04). FLG and IL-17 were higher in the melasma than in the perilesional skin ( P = 0.003). IL-17 and profilaggrin expression were positively associated (R = 0.60, P = 0.04). IL-33 expression was higher in the adjacent normal skin than in the melasma ( P = 0.01). This study found subclinical inflammation in the skin adjacent to the melasma, dysfunction of the epidermal barrier in lesions associated with chronic inflammation, and an abnormal differentiation process promoting an increase in FLG. These findings highlight the need to preserve the integrity of the facial stratum corneum in these patients.

TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence

Itching is a sensory phenomenon characterized by an unpleasant sensation that makes you want to scratch the skin, and chronic itching diminishes the quality of life. In recent studies, multiple transient receptor potential (TRP) channels present in keratinocytes or nerve endings have been shown to engage in the propagation of itch signals in chronic dermatological or pruritic conditions, such as atopic dermatitis (AD) and psoriasis (PS). TRPV3, a member of the TRP family, is highly expressed in the epidermal keratinocytes. Normal TRPV3 signaling is essential for maintaining epidermal barrier homeostasis. In recent decades, many studies have suggested that TRPV3 contributes to detecting pruritus signals. Gain-of-function mutations in TRPV3 in mice and humans are characterized by severe itching, hyperkeratosis, and elevated total IgE levels. These studies suggest that TRPV3 is an important channel for skin itching. Preclinical studies have provided evidence to support the development of TRPV3 antagonists for treating inflammatory skin conditions, itchiness, and pain. This review explores the role of TRPV3 in chronic pruritus, collating clinical and experimental evidence. We also discuss underlying cellular and molecular mechanisms and explore the potential of TRPV3 antagonists as therapeutic agents.

Phospholipase A2 enzymes represent a shared pathogenic pathway in psoriasis and pityriasis rubra pilaris.

Altered epidermal differentiation along with increased keratinocyte proliferation is a characteristic feature of psoriasis and pityriasis rubra pilaris (PRP). However, despite this large degree of overlapping clinical and histologic features, the molecular signatures these skin disorders share are unknown. Using global transcriptomic profiling, we demonstrate that plaque psoriasis and PRP skin lesions have high overlap, with all differentially expressed genes in PRP relative to normal skin having complete overlap with those in psoriasis. The major common pathway shared between psoriasis and PRP involves the phospholipases PLA2G2F, PLA2G4D, and PLA2G4E, which were found to be primarily expressed in the epidermis. Gene silencing each of the 3 PLA2s led to reduction in immune responses and epidermal thickness both in vitro and in vivo in a mouse model of psoriasis, establishing their proinflammatory roles. Lipidomic analyses demonstrated that PLA2s affect mobilization of a phospholipid-eicosanoid pool, which is altered in psoriatic lesions and functions to promote immune responses in keratinocytes. Taken together, our results highlight the important role of PLA2s as regulators of epidermal barrier homeostasis and inflammation, identify PLA2s as a shared pathogenic mechanism between PRP and psoriasis, and as potential therapeutic targets for both diseases.

Bio-engineering a prevascularized human tri-layered skin substitute containing a hypodermis

Severe injuries to skin including hypodermis require full-thickness skin replacement. Here, we bioengineered a tri-layered human skin substitute (TLSS) containing the epidermis, dermis, and hypodermis. The hypodermal layer was generated by differentiation of human adipose stem cells (ASC) in a collagen type I hydrogel and combined with a prevascularized dermis consisting of human dermal microvascular endothelial cells and fibroblasts, which arranged into a dense vascular network. Subsequently, keratinocytes were seeded on top to generate the epidermal layer of the TLSS.The differentiation of ASC into adipocytes was confirmed in vitro on the mRNA level by the presence of adiponectin, as well as by the expression of perilipin and FABP-4 proteins. Moreover, functional characteristics of the hypodermis in vitro and in vivo were evaluated by Oil Red O, BODIPY, and AdipoRed stainings visualizing intracellular lipid droplets.Further, we demonstrated that both undifferentiated ASC and mature adipocytes present in the hypodermis influenced the keratinocyte maturation and homeostasis in the skin substitutes after transplantation. In particular, an enhanced secretion of TGF-β1 by these cells affected the epidermal morphogenesis as assessed by the expression of key proteins involved in the epidermal differentiation including cytokeratin 1, 10, 19 and cornified envelope formation such as involucrin.Here, we propose a novel functional hypodermal-dermo-epidermal tri-layered skin substitute containing blood capillaries that efficiently promote regeneration of skin defects. Statement of significanceThe main objective of this study was to develop and assess the usefulness of a tri-layered human prevascularized skin substitute (TLSS) containing an epidermis, dermis, and hypodermis. The bioengineered hypodermis was generated from human adipose mesenchymal stem cells (ASC) and combined with a prevascularized dermis and epidermis.The TLSS represents an exceptional model for studying the role of cell-cell and cell-matrix interactions in vitro and in vivo. In particular, we observed that enhanced secretion of TGF-β1 in the hypodermis exerted a profound impact on fibroblast and keratinocyte differentiation, as well as epidermal barrier formation and homeostasis. Therefore, improved understanding of the cell-cell interactions in such a physiological skin model is essential to gain insights into different aspects of wound healing.

Decreased Calcium-Sensing Receptor Expression Controls Calcium Signaling and Cell-To-Cell Adhesion Defects in Aged Skin

The calcium-sensing receptor (CaSR) drives essential calcium ion (Ca2+) and E-cadherin‒mediated processes in the epidermis, including differentiation, cell-to-cell adhesion, and epidermal barrier homeostasis in cells and inyoung adult mice. We now report that decreased CaSR expression leads to impaired Ca2+ signal propagation in aged mouse (aged >22 months) epidermis and human (aged >79 years, donor age) keratinocytes. Baseline cytosolic Ca2+ concentrations were higher, and capacitive Ca2+ entry was lower in aged than in young keratinocytes. As in Casr-knockout mice (EpidCaSR-/-), decreased CaSR expression led to decreased E-cadherin and phospholipase C-γ expression and to a compensatory upregulation of STIM1. Pretreatment with the CaSR agonist N-(3-[2-chlorophenyl]propyl)-(R)-alpha-methyl-3-methoxybenzylamine normalized Ca2+ propagation and E-cadherin organization after experimental wounding. These results suggest that age-related defects in CaSR expression dysregulate normal keratinocyte and epidermal Ca2+ signaling, leading to impaired E-cadherin expression, organization, and function. These findings show an innovative mechanism whereby Ca2+- and E-cadherin‒dependent functions are impaired in aging epidermis and suggest a new therapeutic approach by restoring CaSR function.

196 Relationship between the physicochemical effect of compounds on phospholipid membranes and their influence on epidermal permeability barrier homeostasis

Secretion of lipids from lamellar bodies into the intercellular space between stratum granulosum and stratum corneum is a crucial step in epidermal water-impermeable barrier homeostasis. Our previous work showed that topical application of fatty acids, sex hormones, hexoses, polyols and polymers influences barrier homeostasis, but the effects are highly dependent on even small variations of molecular structure. Therefore, we evaluated the effects of these molecules on the physicochemical properties of phospholipid monolayers and liposomes as models of the lamellar body membrane and cell membrane.

Can simple physicochemical studies predict the effects of molecules on epidermal water‐impermeable barrier function?

Improvement of the water-impermeable barrier function of skin is clinically important, because barrier abnormality is associated with various skin diseases, such as psoriasis or atopic dermatitis. We have shown that topical application of fatty acids, sex hormones, hexoses, polyols and polymers influences barrier homeostasis, but the effects are highly dependent on even small variations of molecular structure. Moreover, the effects appear within one hour after application and thus are likely to be non-genomic (physicochemical) phenomena. Secretion of lipids from lamellar bodies into the intercellular space between stratum granulosum and stratum corneum is a crucial step in epidermal water-impermeable barrier homeostasis, especially at the early stage of barrier recovery after damage, and phase transition of the lipid lamellar structure in the epidermis is an important part of this process. Therefore, we evaluated the effects of the above molecules on the physicochemical properties of phospholipid monolayers and liposomes as models of the lamellar body membrane and cell membrane. Molecules that influenced the barrier recovery process also altered the stability of liposomes and the air-water surface pressure of phospholipid monolayers. Studies using attenuated total reflection Fourier-transform infrared spectroscopy (ATR FT-IR), differential scanning calorimetry (DSC) and 13 C nuclear magnetic resonance (NMR) spectrometry suggested that molecules influencing barrier recovery interact specifically with phospholipids. The idea that molecules interacting with phospholipids may influence barrier homeostasis should open up new approaches to the treatment of a variety of skin diseases.

253 Epidermal barrier maintenance and morphogenesis are molecularly distinct and ceramide synthase 4 is a novel key player in epidermal barrier maintenance

Proper establishment and continuous maintenance of the skin epidermal barrier are critical to protect organisms from pathogens and other external stresses. However, how the adult epidermal barrier is maintained and whether disturbed barrier maintenance causes disease is not known. This study illustrates that epidermal barrier morphogenesis and maintenance are molecularly distinct processes. Further we show that adult barrier repair upon damage recapitulates the morphogenetic program. Mechanistically, the stratum corneum protein and protein-bound lipids direct barrier establishment and repair, whereas the lipid matrix dominates homeostatic maintenance. A switch in epidermal ceramide synthase (CerS) expression characterizes the transition between morphogenetic and homeostatic programs, with CerS3 dominating morphogenesis and CerS4 homeostasis. Consequently, CerS4 controls barrier maintenance but is not required for morphogenesis. Epidermal loss of CerS4 disturbs adult epidermal lipid barrier homeostasis, ultimately resulting in skin inflammation, acanthosis, and hyperkeratosis recapitulating features of human skin disease. These studies highlight the molecular specificity of barrier morphogenesis, maintenance and repair and identify disturbances in epidermal lipid metabolism and barrier homeostasis as underlying causes for inflammatory skin disease in adults.

Epidermal mammalian target of rapamycin complex 2 controls lipid synthesis and filaggrin processing in epidermal barrier formation

Perturbation of epidermal barrier formation will profoundly compromise overall skin function, leading to a dry and scaly, ichthyosis-like skin phenotype that is the hallmark of a broad range of skin diseases, including ichthyosis, atopic dermatitis, and a multitude of clinical eczema variants. An overarching molecular mechanism that orchestrates the multitude of factors controlling epidermal barrier formation and homeostasis remains to be elucidated. Here we highlight a specific role of mammalian target of rapamycin complex 2 (mTORC2) signaling in epidermal barrier formation. Epidermal mTORC2 signaling was specifically disrupted by deleting rapamycin-insensitive companion of target of rapamycin (Rictor), encoding an essential subunit of mTORC2 in mouse epidermis (epidermis-specific homozygous Rictor deletion [RicEKO] mice). Epidermal structure and barrier function were investigated through a combination of gene expression, biochemical, morphological and functional analysis in RicEKO and control mice. RicEKO newborns displayed an ichthyosis-like phenotype characterized by dysregulated epidermal de novo lipid synthesis, altered lipid lamellae structure, and aberrant filaggrin (FLG) processing. Despite a compensatory transcriptional epidermal repair response, the protective epidermal function was impaired in RicEKO mice, as revealed by increased transepidermal water loss, enhanced corneocyte fragility, decreased dendritic epidermal T cells, and an exaggerated percutaneous immune response. Restoration of Akt-Ser473 phosphorylation in mTORC2-deficient keratinocytes through expression of constitutive Akt rescued FLG processing. Our findings reveal a critical metabolic signaling relay of barrier formation in which epidermal mTORC2 activity controls FLG processing and de novo epidermal lipid synthesis during cornification. Our findings provide novel mechanistic insights into epidermal barrier formation and could open up new therapeutic opportunities to restore defective epidermal barrier conditions.

Modulation of lipid fluidity likely contributes to the fructose/xylitol-induced acceleration of epidermal permeability barrier recovery.

We previously showed that topical application of hexoses such as fructose accelerates barrier recovery after disruption. We also showed that various hexoses and polyols interact with phospholipid and alter the phase transition temperature. Thus, we hypothesized that the improvement of barrier recovery by hexoses and polyols might be related to the interaction with phospholipid. Here, we tested this idea by examining the effects of xylitol (a component of some skin-care products) and fructose on lipid dynamics in an epidermal-equivalent model at the single-cell level by means of two-photon microscopy after staining with Laurdan, a fluorescent dye sensitive to the physical properties of its membrane environment. First, we confirmed that topical application of xylitol aqueous solution on tape-stripped human skin accelerated barrier recovery. Then, we examined changes of lipid fluidity in the epidermal-equivalent model after application of water or an aqueous solution of xylitol or fructose. Application of xylitol and/or fructose increased the lipid fluidity in the uppermost part of the stratum granulosum layer, compared to treatment with water alone, and accelerated the exocytosis of lamellar bodies to the intercellular domain between stratum corneum and stratum granulosum. Our results support the idea that the improvement of epidermal barrier homeostasis upon topical application of xylitol or fructose is due to increased lipid fluidity in the uppermost layer of the stratum granulosum, which enables accelerated release of lipid from the stratum granulosum, thereby improving the lamellar structure and accelerating epidermal permeability barrier recovery.

Efficient Transdermal Delivery of DNA Nanostructures Alleviates Atopic Dermatitis Symptoms in NC/Nga Mice

AbstractDNA nanostructures have been widely studied in biomedical research contributing to targeted treatment of chronic diseases. The immunostimulatory XL‐DNA nanostructures of X‐shaped oligodeoxynucleotides complex are previously reported, activating toll‐like receptor9 in dendritic cells. This study examines whether the XL‐DNA could be therapeutically applied to treat immune diseases such as atopic dermatitis. To optimize topical delivery, liposome‐encapsulated XL‐DNA (Lipo‐XL‐DNA) is generated using emulsion transfer method with lipid layers composed of 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine, 1,2‐dioleoyl‐sn‐glycero‐3‐phospho‐(1′‐rac‐glycerol), and cholesterol. Size distribution of Lipo‐XL‐DNA ranges around 90–160 nm with mean diameter of 115.44 ± 18.72 nm. The morphology is confirmed by transmission electron microscope. Zeta potential is −28.59 mV. Confocal microscopy shows that Lipo‐XL‐DNA is efficiently delivered into epidermis and dermis. Topical application of Lipo‐XL‐DNA effectively alleviates atopic dermatitis symptoms in mice, as shown by dermatitis score, histological evaluation, and serum immunoglobulin E levels. RNA‐seq analysis confirms that Lipo‐XL‐DNA reduces pro‐inflammatory products, but increases epidermal barrier homeostasis factors in atopic dermatitis lesions. Lipo‐XL‐DNA orchestrates immune balance by downregulating Th2 immunity, but upregulating Th1 immunity. Collectively, liposome encapsulation enables efficient transdermal delivery of XL‐DNA, for an effective treatment of atopic dermatitis in mice. The results provide a promising therapeutic strategy using XL‐DNA nanostructures to treat immune‐compromised diseases.

Peeling Skin Disorders: A Paradigm for Skin Desquamation

Epidermal desquamation is the highly regulated process of invisible shedding of corneocytes from the outermost layers of the stratum corneum. This occurs through the interplay between proteases and their inhibitors that control the degradation of corneodesmosomes. Skin peeling refers to exaggerated visible superficial desquamation and can occur in inherited and acquired conditions. The illumination of the molecular basis of genetic disorders with skin peeling sheds light on the biological mechanisms of epidermal desquamation and skin barrier homeostasis. Proteins that are mutated in peeling skin disorders are components of corneodesmosomes (CDSN, DSG1) or protease inhibitors (LEKTI, CSTA, CAST, or SERPIN8). FLG2 emerged as a new player that regulates epidermal desquamation, as demonstrated by the phenotype observed in patients reported by 2 independent groups.

Endoplasmic Reticulum Calcium Regulates Epidermal Barrier Response and Desmosomal Structure

Ca(2+) fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, and epidermal barrier homeostasis. We previously showed that intracellular Ca(2+) stores constitute a major portion of the calcium gradient especially in the stratum granulosum. Loss of the calcium gradient triggers epidermal barrier homeostatic responses. In this report, using unfixed exvivo epidermis and human epidermal equivalents we show that endoplasmic reticulum (ER) Ca(2+) is released in response to barrier perturbation, and that this release constitutes the major shift in epidermal Ca(2+) seen after barrier perturbation. We find that ER Ca(2+) release correlates with a transient increase in extracellular Ca(2+). Lastly, we show that ER calcium release resulting from barrier perturbation triggers transient desmosomal remodeling, seen as an increase in extracellular space and a loss of the desmosomal intercellular midline. Topical application of thapsigargin, which inhibits the ER Ca(2+) ATPase activity without compromising barrier integrity, also leads to desmosomal remodeling and loss of the midline structure. These experiments establish the ER Ca(2+) store as a master regulator of the Ca(2+) gradient response to epidermal barrier perturbation, and suggest that ER Ca(2+) homeostasis also modulates normal desmosomal reorganization, both at rest and after acute barrier perturbation.

Rab11a Is Essential for Lamellar Body Biogenesis in the Human Epidermis

Most of the skin barrier function is attributable to the outermost layer of the epidermis, the stratum corneum, which is composed of flattened, anucleated cells called corneocytes surrounded by a lipid-enriched lamellar matrix. The composition of the stratum corneum is directly dependent on the underlying granular keratinocytes, which are the last living cells in the stratified epidermis. Many components present in the intercorneocyte matrix are delivered by the underlying granular keratinocytes through a secretion process dependent on lysosome-related organelles called lamellar bodies. Because of the importance of lamellar bodies in the maintenance of the epidermal barrier, the mechanisms regulating their biogenesis must be betterunderstood. In this study, we show that the Rab11a GTPase is highly expressed in terminally differentiated keratinocytes, where it is partly associated with lamellar bodies. Rab11a silencing in three-dimensional invitro reconstructed human epidermis induces a barrier defect, a decrease in the amount of lipid found in the stratum corneum, a reduction in lamellar body density and secretion areas in granular keratinocytes, and the mis-sorting of lamellar body cargoes being driven to the lysosomal degradation pathway. Our results highlight the importance of Rab11a-dependent regulation of lamellar body biogenesis in keratinocytes and consequently on epidermal barrier homeostasis.

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands.

BackgroundProtease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin.ObjectiveTo evaluate the basic physiological role of PAR-2 in skin.MethodsWe investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes.ResultsStrong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker.ConclusionOur data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.

SERPINB3/B4 Contributes to Early Inflammation and Barrier Dysfunction in an Experimental Murine Model of Atopic Dermatitis

Serine proteases are critical for epidermal barrier homeostasis and their aberrant expression and/or activity is associated with chronic skin diseases. Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen in patients with atopic dermatitis and psoriasis. However their mechanistic role in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical Aspergillus fumigatus extract exposure in wild-type and Serpinb3a null mice on transepidermal water loss (TEWL), sensitization and inflammation. Allergen exposure induced Serpinb3a expression in the skin, along with increased TEWL, epidermal thickness, and skin inflammation, all of which were attenuated in the absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression supporting a role for SERPINB3/B4 in initiation of the acute inflammatory response. RNA-Seq analysis following allergen exposure identified a network of pro-inflammatory genes induced in the wild type mice that was absent in the Serpinb3a null mice. In conclusion, Serpinb3a deficiency attenuates barrier dysfunction and the early inflammatory response following cutaneous allergen exposure, supporting a role for Serpinb3a (mice) and SERPINB3/B4 (humans) early in atopic dermatitis.

Skin pH in the Elderly and Appropriate Skin Care

The acidic skin surface pH (pHSS) plays a crucial role in the maintenance of a vital stratum corneum (SC) and an intact epidermal barrier. However, ageing affects the pH of the skin, both pHSS and the pH of the stratum corneum (pHSC). The purpose of this article is to review the physiological function of skin pH and the effects of an age-related increase of skin pH. Moreover, the consequences for the development of skin care products, specifically for the elderly, will be discussed. Reported pHSS values of the skin range between 4 and 6 in non-intertriginous areas. The acidity of the outer surface of the skin is essential regarding the following functions: epidermal barrier homeostasis, integrity/cohesion of the SC, support of proteolytic processes leading to desquamation, metabolism of extracellular lipids, and microbiological colonisation of the SC. Exogenous, as well as endogenous factors, affect skin pH (especially pHSS), thereby influencing its functions. Age is one important endogenous factor. Interestingly, pHSS of adults slightly increases with age. This increase of pHSSinfluences several functions in ageing skin. Increased pHSS may impair epidermal barrier permeability, integrity/cohesion of the SC, and even antimicrobial capacity. Hence, ageing skin shows an increased vulnerability, not only towards mechanical stress. Moreover, aged skin often appears rough and dry, which is sometimes associated with itching. However, so far only a few studies have investigated the effect of skin care products on ageing skin. In addition, normalising the increased skin pH in the elderly by appropriate skin care products formulated with a lower pH, e.g. 4, may improve impaired skin functions, which are impaired.