Expression of the C-C chemokine MIP-3 alpha/CCL20 in human epidermis with impaired permeability barrier function

External assault to the skin is followed by an epidermal response including synthesis of DNA, lipids, cytokines and migration of antigen presenting cells. MIP-3 alpha (CCL20, LARC, Exodus-1, Scya20) is a recently described C-C chemokine, predominantly expressed in extralymphoid tissue, which is known to direct migration of dendritic cell precursors and memory lymphocytes to sites of antigen invasion. We assessed the expression of MIP-3 alpha in human skin using semi-quantitative polymerase chain reaction. In vivo, MIP-3 alpha mRNA was constitutively expressed at low levels in untreated human epidermis. After acute disruption of the epidermal permeability barrier MIP-3 alpha mRNA was upregulated in the epidermal fraction, whereas dermal MIP-3 alpha mRNA levels remained unchanged. In vitro, MIP-3 alpha was increased in cultured keratinocytes treated with IL-1 alpha and TNF-alpha and was present in immature and mature dendritic cells, THP-1 monocytic cells and activated T cells. Finally, skin biopsies from patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant expression. In biopsies from atopic dermatitis and graft vs. host disease a weak signal was present, whereas no expression was found in scleroderma and toxic epidermal necrolysis. We conclude that regulation of MIP-3 alpha mRNA is part of the epidermal response to external assault. Its upregulation may represent a danger signal for increased immunosurveillance in barrier disrupted skin and inflammatory skin conditions with impaired barrier function to counteract potential antigen invasion.     

Acute irritant threshold correlates with barrier function,skin hydration and contact hypersensitivity in atopic dermatitis and rosacea

The aim of the study was to disclose interactions between epidermal barrier, skin irritation and sensitization in healthy and diseased skin. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) were assessed in adult patients with atopic dermatitis (AD), rosacea and healthy controls. A 4‐h patch test with seven concentrations of sodium lauryl sulphate was performed to determine the irritant threshold (IT). Contact sensitization pattern was revealed by patch testing with European baseline series. Subjects with a lower IT had higher TEWL values and lower SCH. Subjects with positive allergic reactions had significantly lower IT. In AD, epidermal barrier deterioration was detected on both volar forearm and nasolabial fold, while in rosacea, impeded skin physiology parameters were observed on the facial skin only, suggesting that barrier impediment is restricted to the face in rosacea, in contrast with AD where the abnormal skin physiology is generalized.     

Effects of site and menstrual cycle on barrier function and stratum corneum water-holding capacity

Background/aims: Areas of the skin with similar anatomical structure may have different functional behaviour. In vivo barrier function and stratum corneum water-holding capacity during the menstrual cycle on two sites of the volar forearm (upper and lower) and on the anterior aspect of the thigh were evaluated using the plastic occlusion stress test (POST).
Methods: 13 healthy women (age 31 ± 4) with regular menses entered the study. POST was performed by applying a plastic chamber (1.8 cm diameter) on the skin for 24 h. After removal the skin surface water loss (SSWL) was measured using an evaporimeter (EP1-Servomed, Sweden) every 5 min for 30 min. Measurements were taken on the 10th and 25th day of the menstrual cycle. Statistical analysis was performed using one-factor A nova for repeated measures. Free and bound water compartments of evaporation were also analysed.
Results: Higher hydration and SSWL were detectable on the 25th day of the cycle. However, no significant influence of menstrual cycle was found. Significant differences between the upper and lower volar foream were detected ( P < 0.001).
Conclusion: The differences observed were mainly related to the evaporation of bound water, confirming a different barrier function at the sites investigated; therefore, it must be taken into account that adjacent skin sites with equal structure may have different functional behaviour.     

Repair of acetone- and sodium lauryl sulphate-damaged human skin barrier function using topically applied emulsions containing barrier lipids

BACKGROUND: It is generally acknowledged that well-formulated moisturizing skin care products can restore disturbed barrier function that can be assessed by transepidermal water loss (TEWL) measurements. When ceramides and/or other barrier lipids are incorporated, it is, however, not always clearly demonstrated which ingredients of the formulation exert the beneficial effects. OBJECTIVES: In this study the effects of topically applied ceramide-containing mixtures on the barrier repair of sodium lauryl sulphate (SLS)- and acetone-induced skin damage have been studied in human volunteers. TEWL and stratum corneum hydration measurements were carried out. The emulsions applied contained either a mixture of two types of ceramides, CerIII and CerIIIB (emulsion 1) or a complete mixture of ceramides III, IIIB and VI together with phytosphingosine, cholesterol and the free fatty acid linoleic acid (emulsion 2). RESULTS: After SLS damage, it was observed that barrier recovery was significantly accelerated by topical application (14 days, 2 x/d) of emulsion 2 compared with the results obtained with emulsion 1. Corneometrical results were not relevant due to the occurrence of scaly fissured skin, failing to provide a good skin/probe contact. Although no effect on TEWL could be observed, the improvement of skin hydration after acetone treatment and a single application of the emulsions, was significantly more positive for emulsion 2 than for emulsion 1. CONCLUSIONS: The investigative methods used in this study show that ceramides combined with other skin lipids can improve barrier repair after damage.     

Disruption of barrier function in dermatophytosis and pityriasis versicolor

Dermatophytes have the ability to form molecular attachments to keratin and use it as a source of nutrients, colonizing keratinized tissues, including the stratum corneum of the skin. Malassezia species also affect the stratum corneum of the skin. Therefore, dermatophytosis and pityriasis versicolor of the skin are thought to be important factors of profound changes in skin barrier structure and function. We aimed to describe the changes in transepidermal water loss (TEWL), stratum corneum hydration, and skin pH in the lesions of the dermatophytosis and pityriasis versicolor. Thirty-six patients with dermatophytosis (14 with tinea cruris, 13 with tinea corporis and nine with tinea pedis or tinea manus) and 11 patients with pityriasis versicolor were included in this study. TEWL, stratum corneum conductance and skin pH were determined by biophysical methods to examine whether our patients exhibited changes in barrier function. Dermatophytosis and pityriasis versicolor except tinea pedis and tinea manus showed highly significant increase in TEWL compared with adjacent infection-free skin. Hydration was significantly reduced in lesional skin compared with adjacent infection-free skin. From this study, infections with dermatophytes and Malassezia species on the body can alter biophysical properties of the skin, especially the function of stratum corneum as a barrier to water loss. On the contrary, infections with dermatophytes on the palms and soles little affect the barrier function of the skin.     

Semipermeable glove membranes–effects on skin barrier repair following SLS irritation

Background: Transepidermal water flux is the regulatory signal for barrier regeneration.
Objective: In this study, we evaluated the impact of glove membranes, which provide a partial barrier and different water loss rates, on barrier recovery after standardized irritation with sodium lauryl sulfate (SLS).
Methods: Twenty-five healthy volunteers were irritated for 24 hr with SLS 1%. Four test areas were marked on clinically normal skin on the upper back. Barrier repair under consecutive dressing with semipermeable membranes (GoreTex^®, Sympatex^®), an occlusive membrane (Meditrate Vinyl^®), and in an uncovered control area were evaluated by measurements of transepidermal water loss (TEWL) and erythema (a*).
Results: Areas semipermeably covered showed an enhanced barrier recovery and a reduced inflammatory response compared to the area under occlusion and the control. During healing process, TEWL ( P < 0.01) and a* ( P < 0.001) values were significantly lower in areas semipermeably covered than in the vinyl covered area and in the control.
Conclusions: The results support the hypothesis that semipermeable materials improve barrier recovery rates by providing an optimized water vapour gradient during the healing process. This underlines the unique benefit of semipermeable gloves in the prevention of occupational skin disease: (i) by minimizing glove-induced irritation and (ii) by enhancing barrier recovery through protective glove materials at the work place in cases of pre-existing minor irritant dermatitis.     

Recovery of skin barrier function in psoriasis following standardized trauma

Following a standardized trauma to the clinically uninvolved skin of psoriatic patients, an overresponse of several metabolic processes occurs. In the present study, barrier functions of normal looking skin of psoriatic patients and healthy controls were assessed during 5 weeks following a standardized injury. Surprisingly, recovery rates of both groups proved to be identical. The significance of this finding in the epidermal homeostasis of psoriasis is discussed.     

Occlusion vs. skin barrier function

Background/aims: Skin occlusion may increase percutaneous absorption of applied chemicals, with some exceptions. It also obstructs the normal ventilation of the skin surface and increases stratum corneum hydration and hence compromises skin barrier function.
Methods/results: This review focuses the effects of occlusion on skin barrier function, in particularly, as defined with objective skin bioengineering technology.
Conclusions: The effects of occlusion on skin barrier function have been defined with various techniques. Optimal hydrocolloid materials can absorb excess water and reduce the unfavourable effects of occlusion.     

Epidermal proliferative response induced by sodium dodecyl sulphate varies with environmental humidity

BACKGROUND: Previous studies have suggested that susceptibility of skin to external agents increases in the dry winter season. OBJECTIVES: To test the hypothesis that environmental humidity affects skin sensitivity to irritants. METHODS: The epidermal hyperplasia induced by sodium dodecyl sulphate (SDS) under various humidity conditions was evaluated on the skin of hairless mice. RESULTS: Mice kept under low humidity for 2 days showed more obvious epidermal proliferation 24 h after topical application of SDS than those kept under high or normal humidity for 2 days. In contrast, mice kept under high humidity for 2 weeks showed more obvious epidermal proliferation 24 h after topical application of SDS than those kept under low or normal humidity. The transepidermal water loss was altered significantly in the animals kept under high humidity for 2 weeks, although it was not altered during the first 7 days under either low or high humidity. CONCLUSIONS: These results suggest that environmental humidity influences the sensitivity of skin to topical application of SDS and that increased sensitivity is not always associated with alteration of the water impermeability of the stratum corneum.     

Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial

BACKGROUND: Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. OBJECTIVES: To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. METHODS: Volunteers (n = 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. RESULTS: Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. CONCLUSIONS: Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level.     

Effect of semipermeable membranes on skin barrier repair following tape stripping

Abstract  Reports in the literature suggest that the permeability of a wound dressing to water transport is an important variable in the healing of superficial wounds. Factors that influence skin hydration during barrier repair, therefore, are important in the optimization of wound treatments. In this study, the effects of semipermeable films on human skin following a standardized wound (tape stripping) were evaluated using measurements of transepidermal water loss (TEWL), skin hydration, rate of moisture accumulation, and erythema. Wounds treated with semipermeable films underwent more rapid barrier recovery than either unoccluded wounds or wounds under complete occlusion. Barrier films that produced intermediate levels of skin hydration during recovery produced the highest barrier repair rates. The results support the hypothesis that semipermeable wound dressings augment barrier repair and skin quality by providing an optimized water vapor gradient during the wound healing process. The choice of wound dressing is discussed within the larger context of the design of vapor-permeable fabrics (smart materials) and the new fields of corneotherapy and comfort science. Received: 19 April 2001 / Revised: 2 June 2001 / Accepted: 16 September 2001     

Efficacy of skin barrier creams (IV). The repetitive irritation test (RIT) with a set of 4 standard irritants

An improved human model for the quantification of skin barrier creams (BCs) is described. In contrast to the previously published procedure, the back, instead of the forearm, and a total of 4 irritants are used. Due to the larger area, 3 BC formulations can be simultaneously compared to the control field, which receives the irritant only, without BC-pretreatment. On 10 human volunteers, the irritants 10% sodium lauryl sulfate (SLS), 1% sodium hydroxide (NaOH), 30% lactic acid (LA) and undiluted toluene (TOL) were applied via large Finn Chambers for 30 min, 5 × during the 1st week and 4 × during the 2nd week. Taktosan Salbe (water-in-oil emulsion) and RAWI Speerschutzcreme (oil-in-water emulsion) were applied 30 min before contact with the irritants. In order to asses reproducibility and interindividual variation, the BC RAWI was tested in duplicate. Irritant cutaneous reactions were quantified by 4 parameters: erythema score, transepidermal water loss, blood flow volume and stratum corneum hydration by measuring capacitance. The results showed marked differences in efficacy. Taktosan significantly suppressed irritation by SLS, NaOH and LA, which was apparent in nearly all parameters. RAWI caused significant inhibition of SLS irritation, and a positive trend against NaOH and LA was observed. Both BCs failed against TOL. The results of duplicate testing with RAWI showed good reproducibility. The dogma that oil-in-water emulsions are primarily effective against lipophilic irritants, and water-in-oil emulsions against hydrophilic irritants, needs to be re-evaluated on the basis of our findings. This model seems to have potential for further studies on BCs and might elucidate the complex interaction of BCs with irritants.     

International guidelines for the in vivo assessment of skin properties in non‐clinical settings: Part 2. transepidermal water loss and skin hydration

Background

There is an emerging perspective that it is not sufficient to just assess skin exposure to physical and chemical stressors in workplaces, but that it is also important to assess the condition, i.e. skin barrier function of the exposed skin at the time of exposure. The workplace environment, representing a non‐clinical environment, can be highly variable and difficult to control, thereby presenting unique measurement challenges not typically encountered in clinical settings.

Methods

An expert working group convened a workshop as part of the 5th International Conference on Occupational and Environmental Exposure of Skin to Chemicals (OEESC) to develop basic guidelines and best practices (based on existing clinical guidelines, published data, and own experiences) for the in vivo measurement of transepidermal water loss (TEWL) and skin hydration in non‐clinical settings with specific reference to the workplace as a worst‐case scenario.

Results

Key elements of these guidelines are: (i) to minimize or recognize, to the extent feasible, the influences of relevant endogenous‐, exogenous‐, environmental‐ and measurement/instrumentation‐related factors; (ii) to measure TEWL with a closed‐chamber type instrument; (iii) report results as a difference or percent change (rather than absolute values); and (iv) accurately report any notable deviations from this guidelines.

Conclusion

It is anticipated that these guidelines will promote consistent data reporting, which will facilitate inter‐comparison of study results.     

Barium sulphate with a negative zeta potential accelerates skin permeability barrier recovery and prevents epidermal hyperplasia induced by barrier disruption

BACKGROUND: Barium sulphate, a stable inorganic material, has been used in contrast media and cosmetic products because of its stability. As a negative external electric potential accelerates the skin barrier repair after barrier disruption, we hypothesized that topical application of barium sulphate may affect the skin barrier recovery rate depending on its zeta potential. OBJECTIVES: To investigate whether barium sulphate particles in aqueous solution have different zeta potentials depending on their surface structure, and to investigate the possible relation between zeta potential and skin barrier recovery rate. METHODS: Mice were subjected to tape stripping to disrupt barrier function, or were treated with acetone and kept in a dry environment to induce epidermal hyperplasia. They were then treated with different forms of barium sulphate, and barrier recovery was monitored by measurements of transepidermal water loss. RESULTS: There was a significant correlation between the barrier recovery rate and zeta potential of barium sulphate applied topically. Barium sulphate with a negative zeta potential significantly accelerated barrier recovery, but barium sulphate with a positive zeta potential did not accelerate or even delayed barrier repair. Barium sulphate with a negative zeta potential had an X-ray diffraction pattern different from that with a positive potential. The distribution of calcium in the epidermis was also influenced by the polarity of zeta potential. CONCLUSIONS: These findings suggest a new pharmacological approach towards altering barrier function or epidermal hyperplasia with inorganic particles in healthy and diseased skin.     

Skin hydration and transepidermal water loss in patients with a history of sulfur mustard contact: a case–control study

Background   Skin lesions are among the most common complications of contact with sulfur mustard.
Objective   This study was aimed to measure skin water content and transepidermal water loss (TEWL) in patients with a history of sulfur mustard contact.
Methods   Three hundred ten male participants were included in this study: 87 (28.1%) sulfur mustard–exposed patients with current skin lesions (group 1), 71 (22.9%) sulfur mustard–exposed patients without skin lesions (group 2), 78 (25.2%) patients with dermatitis (group 3) and 74 (23.8%) normal controls (group 4) The water content and TEWL of skin was measured at four different locations of the body: forehead, suprasternal, palm and dorsum of hand. Nonparametric statistical tests (Kruskal–Wallis) were used to compare the four groups, and P  < 0.05 was considered statistically significant.
Results   The mean age of participants were 44.0 ± 6.7, 41.9 ± 5.9, 43.8 ± 9.3 and 44.8 ± 8.9 years in groups 1 to 4, respectively ( P  = 0.146). Xerosis, post-lesional hyperpigmentation and lichenification were significantly more common in either sulfur mustard–exposed participants or non-exposed participants with dermatitis ( P  < 0.05). Skin hydration was higher in subjects with sulfur mustard contact than in non-injured participants ( P  < 0.05) in the dorsum and palm of hands and forehead. TEWL was significantly higher in participants only in suprasternal area and dorsum of hand.
Conclusion   Contact with sulfur mustard agent can alter biophysical properties of the skin-especially the function of stratum corneum as a barrier to water loss-several years after exposure.

Conflicts of interest

None declared.     

Biophysical characteristics of skin in diabetes: a controlled study

Background  Cutaneous complications are common in diabetes. Previous assays suggest that hyperglycemia and decreased insulin signal are involved in the impairment of skin function. The aim of this study was to evaluate the biophysical characteristics of skin in patients with diabetes mellitus and compares them with healthy non-diabetic controls.
Objective  To measure biophysical characteristic of skin including transepidermal water loss (TEWL), water content, sebum and skin elasticity in patients with diabetes mellitus and compare them with healthy non-diabetic controls.
Methods  This case-control study was conducted on 38 patients with diabetes and 40 age- and sex-matched healthy people. The biophysical properties of skin including stratum corneum (SC) hydration, sebum content, TEWL and skin elasticity were measured and compared between the two groups at three different locations of the body.
Results  The measurement of SC hydration and TEWL showed no significant difference between diabetics and controls. The skin surface lipids on the forehead but not other sites were significantly lower in the diabetics than in the controls. Acoustic wave propagation speed, a measurement related to skin elasticity, was significantly lower in forearm and forehead of diabetics.
Conclusion  Diabetes affects some functional properties of epidermis and dermis that may responsible for many cutaneous manifestations of diabetes. These results suggest that patients with diabetes mellitus tend to show a normal hydration state of the SC together with decreased sebaceous gland activity and impaired skin elasticity, without any impairment of the SC barrier function.

Conflicts of interest

None declared     

Topical apigenin improves epidermal permeability barrier homoeostasis in normal murine skin by divergent mechanisms

The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In this study, we first determined whether topical apigenin positively influences permeability barrier homoeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice daily for 9 days. At the end of the treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homoeostasis after tape stripping, although basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were upregulated by apigenin. Finally, both cathelicidin‐related peptide and mouse beta‐defensin 3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels and impaired antimicrobial defenses, such as atopic dermatitis.