Distinct locational differences observable in biophysical functions of the facial skin: with special emphasis on the poor functional properties of the stratum corneum of the perioral region

The face is composed of complicated anatomical components, presenting unique portions, such as the eyes, nose and mouth in a relatively narrow area. Moreover, the facial skin is densely populated by the pilosebaceous units and sweat glands, and its stratum corneum (SC) is much thinner than that of the trunk and limbs, although it is always exposed to the environment. Among various portions of the facial skin, some are more easily irritated than others by environmental stimuli, or are more often affected by certain dermatoses. However, the functional aspects of the different portions of the facial skin have not been studied in detail under a strictly controlled environment in sufficiently large numbers of subjects covering different age groups. Thus, we conducted studies in winter with various biophysical techniques, such as transepidermal water loss (TEWL), as a parameter for SC barrier function, high-frequency conductance as that for skin surface hydration state, skin surface lipids, pH, blood flow and skin surface temperature on the forehead, mid-portion of the cheek (cheek in short), nasal tip (nose in short), nasolabial fold and chin of 20 healthy Japanese females aged 22-37 years (average 25 years) in a climate chamber adjusted to 21 degrees C and 50% relative humidity. Thereafter, we studied the influence of ageing on these biophysical parameters by collecting data of TEWL, high-frequency conductance and size of superficial corneocytes on the cheek, nasolabial fold and chin of 303 healthy Japanese female volunteers of different ages. The obtained results showed that the barrier function of the SC was best on the cheek, presenting the lowest TEWL, which was significantly higher on the nasolabial fold and chin than on the cheek. TEWL showed a decrease with age. In contrast, skin hydration state was higher on the nose, but it tended to be lower on the nasolabial fold, showing a mild age-related increase. The corneocytes on the nasolabial fold and chin were smaller than those on the cheek. They revealed a clear increase in size with age. Skin surface lipids were richest on the nose, whereas the superficial pH on the nose was the lowest among the regions tested. The skin temperature was lowest on the cheek than on other areas of the face; although, together with the nose, its blood flow was higher than that of the others. These data indicate great regional differences observable in SC functions on the face. In general, the SC barrier function increases with age, probably because of a decreased epidermal turnover rate as recognized by the increase in corneocyte size. Among the various sites, the skin of the nasolabial fold and chin, whose SC consisted of the smallest corneocytes, showed poorest SC properties in barrier function, suggesting the presence of mild invisible inflammation. It is understandable that this area easily develops not only the complaint of sensitive skin to cosmetics but also dermatitis because of various external agents.     

Effects of topical gluco-oligosaccharide and collagen tripeptide F in the treatment of sensitive atopic skin

Sensitive skin is a dermatological problem of increasing incidence in western countries and is sometimes associated with atopic condition and bacterial sovrainfection. The purpose of this study is to evaluate in a double blind, randomized, placebo controlled trial the efficacy of gluco-oligosaccharide and collagen tripeptide F in controlling the signs and symptoms of sensitive atopic skin. Forty female subjects (age, 30–59 years) affected by non-lesional atopic sensitive skin entered the study. Skin sensitivity was determined by a dermatologist on the basis of medical history, stinging test, dermatological examination and a questionnaire. A treatment with the test products (active and placebo) was carried out for 4 weeks. Measurements and clinical evaluation were carried out at baseline and at the end of the study. The following objective parameters investigated were bacterial count, skin pH and colour, transepidermal water loss (TEWL), stratum corneum hydration, skin roughness and mechanical properties. Clinical assessment included also a scoring system for dryness, desquamation, irritation, erythema and papules. Significant differences were found in the active treated group when compared with the placebo and in particular for instrumental parameters of roughness ( P  < 0.02), volume ( P  < 0.01), TEWL ( P  < 0.02), erythema ( P  < 0.0006) and clinical parameters of dryness, desquamation and irritation ( P  < 0.001). Moisturization levels and skin colour improved significantly in both the active and placebo groups. In conclusion, the study shows that the modulation of bacterial proliferation and normalization of skin barrier properties and stratum corneum moisturization can improve the symptoms of sensitive skin.     

Age‐related changes in skin barrier function – Quantitative evaluation of 150 female subjects

The protection against water loss and the prevention of substances and bacteria penetrating into the body rank as the most important functions of the skin. This so‐called ‘skin barrier function’ is the natural frontier between the inner organism and the environment, and is primarily formed by the epidermis. An impairment of the skin barrier function is often found in diseased and damaged skin. An influence of ageing on skin barrier function is widely accepted, but has not been conclusively evaluated yet. Therefore, the aim of this clinical study was to assess the potential influence of ageing on skin barrier function, including transepidermal water loss (TEWL), stratum corneum hydration, sebum content and pH value. One hundred and fifty healthy women aged 18–80, divided into five age groups with 30 subjects each, were evaluated in this study. TEWL, hydration level, sebum secretion and pH value of hydro‐lipid acid film were measured with worldwide acknowledged biophysical measuring methods at cheek, neck, décolleté, volar forearm and dorsum of hand. Whereas TEWL and stratum corneum hydration showed only very low correlation with subject's age, the sebum production decreased significantly with age, resulting in the lowest skin surface lipids levels measured in subjects older than 70 years. The highest skin surface pH was measured in subjects between 50 and 60 years, whereas the eldest age group had the lowest mean pH. The dorsum of the hand was the location with the highest TEWL and lowest stratum corneum hydration in all age groups. The results show that only some parameters related to skin barrier function are influenced by ageing. Whereas sebum production decreases significantly over lifetime and skin surface pH is significantly increased in menopausal woman, TEWL and stratum corneum hydration show only minor variations with ageing.     

Location‐related differences in structure and function of the stratum corneum with special emphasis on those of the facial skin

Between the two different kinds of the skin covering the body, the glabrous skin is found only on the palmo‐plantar surface because of its rather simple function to protect the underlying living tissue with its remarkably thick stratum corneum (SC) from strong external force and friction. Thus, its barrier function is extremely poor. In contrast, the hair‐bearing skin covers almost all over the body surface regardless of the presence of long hair or vellus hair. In regard to its SC, many dermatologists and skin scientists think that it is too thin to show any site‐specific differences, because the SC is just present as an efficient barrier membrane to protect our body from desiccation as well as against the invasion by external injurious agents. However, there are remarkable regional differences not only in the living skin tissue but also even in such thin SC reflecting the function of each anatomical location. These differences in the SC have been mostly disclosed with the advent of non‐invasive biophysical instruments, particularly the one that enables us to measure transepidermal water loss (TEWL), the parameter of the SC barrier function, and the one that evaluates the hydration state of the skin surface, the parameter of the water‐holding capacity of the SC that brings about softness and smoothness to the skin surface. These in vivo instrumental measurements of the SC have disclosed the presence of remarkable differences in the functional properties of the SC particularly between the face and other portions of the body. The SC of the facial skin is thinner, being composed of smaller layers of corneocytes than that of the trunk and limbs. It shows unique functional characteristics to provide hydrated skin surface but relatively poor barrier function, which is similar to that observed in retinoid‐treated skin or to that of fresh scar or keloidal scars. Moreover, there even exist unexpected, site‐dependent differences in the SC of the facial skin such as the forehead, eyelid, cheek, nose and perioral regions, although each location occupies only a small area. Between these locations, the cheek shows the lowest TEWL in contrast to the perioral region that reveals the highest one. Moreover, these features are not static but change with age particularly between children and adults and maybe also between genders. Among various facial locations, the eyelid skin is distinct from others because its SC is associated with poor skin surface lipids and a thin SC cell layer composed of large corneocytes that brings about high surface hydration state but poor barrier function, whereas the vermillion borders of the lips that are covered by an exposed part of the oral mucosa exhibit remarkably poor barrier function and low hydration state. Future studies aiming at the establishment of the functional mapping in each facial region and in other body regions will shed light on more delicate site‐dependent differences, which will provide us important information in planning the strategy to start so called tailor‐made skin care for each location of the body.     

Methodology to improve epidermal barrier homeostasis: How to accelerate the barrier recovery?

Good water-impermeable barrier function is vital for healthy skin. Abnormality of the barrier function is observed in a variety of skin diseases, such as atopic dermatitis, psoriasis and contact dermatitis. Moreover, repeated barrier disruption induces epidermal hyperplasia and inflammation. On the other hand, acceleration of the barrier recovery prevents epidermal hyperplasia induced by barrier disruption in a dry environment. Thus, methods to improve the barrier function are very important for clinical dermatology. Recently, we have been searching for new reagents and/or new materials to improve barrier homeostasis. In this review, I will describe our recent findings and show how they provide the basis for a new perspective for clinical dermatology.     

Filaggrin – revisited

Profilaggrin (proFLG) and its processing products are critical to the health and appearance of skin. The recent identification of loss‐of‐function filaggrin (FLG) mutations as a predisposing factor in ichthyosis vulgaris and atopic dermatitis has lead to a resurgent interest in this enigmatic protein. Here, we review the literature on the structure and many functions of proFLG, from its role as a filament‐aggregating protein and a source of natural moisturizing factor (NMF), to the more recent discoveries of its role in epidermal barrier formation and its more speculative functions as an antimicrobial and sunscreen. Finally, we discuss the relationship of proFLG with dry skin, the influence of moisturizers on NMF generation and speculate on next generation of FLG research.     

Influence of topically applied ceramide/phospholipid mixture on the barrier function of intact skin, atopic skin and experimentally induced barrier damage

The influence of a liposomal formulation of a ceramide/phospholipid mixture on the barrier function of the skin in atopic tests, in subjects with healthy skin, and after lipid extraction was tested. The transepidermal water loss and the stratum corneum hydration served as parameters for the evaluation of the influence of the ceramide/phospholipid-mixture treatment on the barrier function. Additionally a barrier-function test with nicotinic acid ester was performed after ceramide/phospholipid-mixture application. Stabilizing effects on the barrier function after application of ceramide/phospholipid-mixture were found only in atopic skin and after lipid extraction but not in healthy skin. The results lead us to expect positive effects of ceramide/phospholipid-mixture only if barrier damage is present.     

Material design using genetic algorithms and preparation of innovative UV-reflecting composite

The neck is a sun-exposed area. It seems to show the symptoms of photo-ageing as well as facial skin in the elderly. However, the physiological study of neck skin has hardly been reported. We examined the change of skin physiological properties at a neck site with ageing for 61 women (18—69 years old) compared with a cheek site. Water content in stratum corneum (SC) was higher, transepidermal water loss (TEWL) was lower and the turnover rate of SC judged from corneocyte area was slower at the neck site compared with the cheek site. Skin thickness was thinner, skin extensibility and elasticity were higher, skin grooves were deeper, and anisotropy of skin furrows was lower at the neck site than those at the cheek site. It was shown that the neck was also affected by sunlight but not so much as the cheek from the result of gelatinase activity detected in the tape stripped SC. Skin elasticity decreased with ageing at the neck site as well as the cheek site. Fine wrinkles were remarkably increased in the direction of Langer's line with ageing at the neck. Most skin physiological parameters at the neck showed the value between the cheek (heavily sun-exposed area) and back (not sun-exposed area). From these results, it was considered that not only intrinsic ageing but also photo-ageing affected the neck skin. We developed the prototype of cosmetics corresponding to neck skin physiology based on these results, and evaluated the effectiveness of the prototype product by a consumer test including skin measurement for 4 weeks. After treatment, water content increased, and it gave satisfaction in the skin colour brightness, skin elasticity and skin texture improvements for almost all volunteers. It was concluded that the prototype product was useful in neck skin treatment.     

In vivo barrier challenge and long‐term recovery in human facial skin

Recently, we developed a biophysical approach to characterize in vivo facial cheek skin as a function of stratum corneum (SC) depth, barrier function and during a 24‐h recovery period. The current study extends this work and characterizes the human facial cheek after barrier challenge and, for the first time, facial SC barrier recovery over a 4‐week period. Changes in the corneocyte size over the 4‐week recovery period, and correlations with changes in Trans‐Epidermal Water Loss (TEWL) were monitored. This approach allows complete characterization of SC barrier function after a full biological regeneration of the SC barrier following tape stripping. The structural and compositional changes in facial cheek were investigated using Attenuated Total Reflectance‐Fourier Transform Infra Red (ATR‐FTIR) spectroscopy, tape stripping, TEWL measurements and image analysis combined with optical microscopy to characterize the SC depth profile during the tape stripping stress and over 4‐week recovery period. TEWL increased significantly from baseline after sequential tape stripping. Corneocyte size decreased with successive tape stripping. An inverse direct correlation was determined between TEWL and corneocyte surface area. After 4 weeks, the corneocyte size and TEWL for the facial cheek recovered 100% from the tape stripping procedure. The in vivo ATR‐FTIR data demonstrated that lipid and sebum components on the surface of the facial cheek SC recovered within 24 h post tape stripping, whereas protein (Amide II) and water components recovered after 1 week.     

Lacticaseibacillus paracasei K71 Alleviates UVB-Induced Skin Barrier Dysfunction by Attenuating Inflammation via Increased IL-10 Production in Mice

Scope

Ultraviolet B (UVB) radiation causes skin barrier dysfunction, leading to decreased water-holding capacity, impaired epidermal barrier function, and increased skin thickness. This study investigates the protective effects of oral administration of Lacticaseibacillus paracasei K71 against skin barrier dysfunction in UVB-irradiated mice.

Methods and results

Mice are fed diets with or without K71 and irradiated with UVB three times a week for 12 weeks. Oral administration of K71 suppresses UVB-induced decrease in stratum corneum water content, mitigates the increase of transepidermal water loss, and decreases epidermal thickness of the dorsal skin. Treatment with K71 reverses the upregulation of inflammatory cytokines and the activation of nuclear factor-κB induced by UVB irradiation and upregulates the expression of anti-inflammatory IL-10 in the dorsal skin. Notable upregulation of IL-10 is observed in the spleens of K71-treated mice. K71 treatment enhances IL-10 production in J774.1 macrophages; however, this enhancement is diminished by inhibiting K71 phagocytosis and TLR3. Furthermore, transfection using K71 RNAs significantly increases IL-10 production.

Conclusion

These results indicate that K71 may alleviate UVB-induced skin barrier dysfunction by attenuating inflammation via increasing IL-10 production and that K71 RNAs may induce IL-10 production in macrophages. Therefore, K71 may be beneficial for preventing skin barrier dysfunction.     

Seasonal influences on stratum corneum ceramide 1 fatty acids and the influence of topical essential fatty acids

Ceramide 1 is the main repository of stratum corneum linoleic acid, and changes in the levels of ceramide 1 linoleate are associated with cutaneous abnormalities: essential fatty acid deficiency, atopic dermatitis and acne. We have previously reported seasonal variation in stratum corneum lipids where lipids, particularly ceramides, are very much reduced in winter which probably influences the appearance of skin xerosis in this season. However, investigations into the seasonal variation in ceramide 1 fatty acid levels and the effects of topical essential fatty acids on the composition of these lipid species have not been conducted in healthy subjects. We determined the composition of stratum corneum ceramide 1 esterified fatty acids in leg skin from Caucasian women in winter and summer and also investigated the effects of topical triglycerides rich in linoleic acid on stratum corneum ceramide 1 fatty acid levels in winter. A dramatic seasonal variation was observed. Whereas decreased levels of linoleic acid and some saturated fatty acids (C-15 and C-24) were observed in the winter months, increased levels of oleic acid were found. Nevertheless, it was possible to normalize the levels of stratum corneum ceramide 1 linoleate following topical application of formulations containing linoleic acid-rich triglycerides for 4 weeks. The reduction in ceramide 1 linoleate may lead to impaired stratum corneum function and increased susceptibility to skin xerosis in winter. However, by using formulations containing linoleic acid esters it is possible to correct these changes and possibly improve barrier resilience.     

Inhibitory effect of phosphatidylserine on atopy-like dermatitis in NC/Nga mice

In the present study, the anti-atopic effect of phosphatidylserine (PS) extracted from soybean was investigated in NC/Nga mice. The atopic symptoms were evaluated by scoring spontaneous scratching behavior and skin lesions, by measuring serum levels of immunoglobulin E (IgE) and interleukin-4 (IL-4), and by observing skin histology. After observing the maximum severity of atopic symptoms, PS was initiated. The PS treatment significantly alleviated apparent symptoms of atopic dermatitis and scratching behavior. The suppression of atopic dermatitis by PS was verified by decreases in the serum levels of IgE (p<0.05 after 8 weeks; p<0.001 after 9 weeks) and IL-4 (p<0.01 after 7 weeks; p<0.001 after 9 weeks). Histological observations also indicated that the thickening process of skin and the infiltration of inflammatory cells were significantly inhibited. Taken together, PS from soybean might be useful for alleviating atopic dermatitis symptoms and thus for developing a new medicine for treating human atopic disease.     

Infant skin physiology and development during the first years of life: a review of recent findings based on in vivo studies

Infant skin is often presented as the cosmetic ideal for adults. However, compared to adult skin it seems to be more prone to develop certain pathological conditions, such as atopic dermatitis and irritant contact dermatitis. Therefore, understanding the physiology of healthy infant skin as a point of reference is of interest both from the cosmetic as well as from the clinical point of view. Clinical research on healthy infants is, however, limited because of ethical considerations of using invasive methods and therefore until recently data has been scarce. Technical innovations and the availability of non‐invasive in vivo techniques, such as evaporimetry, electrical impedance measurement, in vivo video and confocal microscopy, and in vivo fibre‐optic based spectroscopy, opened up the field of in vivo infant skin physiology research. Studies incorporating such methods have demonstrated that compared to adult, infant skin continues to develop during the first years of life. Specifically, infant skin appears to have thinner epidermis and stratum corneum (SC) as well as smaller corneocytes at least until the second year of life. The water‐handling properties are not fully developed before the end of the first year and infant SC contains more water and less amounts of natural moisturizing factors. Such findings re‐evaluate the old notions that skin is fully matured at birth. Armed with this knowledge, we are in a position not only to better understand infant dermatological conditions but also to design better skin care products respecting the distinct qualities of infant skin.     

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria—a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the ‘skin barrier/ microbiota/ immune system’ axis and their role in the development of competent functional integrity of the epidermal barrier.     

Health Effects of Probiotics on the Skin

Skin is the largest organ of the body and is constantly exposed to physical, chemical, bacterial, and fungal challenges. It is well known that probiotics are helpful for specific disorders and different clinical studies have indicated that probiotics have special effects in cutaneous apparatus directly or indirectly that can be considerable from versatile aspects. Probiotic bacteriotherapy can have great potential in preventing and treating the skin diseases including eczema, atopic dermatitis, acne, and allergic inflammation or in skin hypersensitivity, UV-induced skin damage, wound protection, and as a cosmetic product. The current paper comprehensively reviews the different health effects of probiotics on the skin.     

Effects of ingesting milk fermented by Lactococcus lactis H61 on skin health in young women: A randomized double-blind study

We conducted a randomized double-blind trial to evaluate the effects of fermented milk produced using only Lactococcus lactis strain H61 as a starter bacterium (H61-fermented milk) on the general health and various skin properties of young women. Healthy female volunteers (n = 23; age = 19–21 r) received H61-fermented milk (10¹⁰ cfu of strain H61/d) or conventional yogurt (10¹⁰ cfu of both Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus per day), as a reference food, daily for 4 wk. Before and at the end of 4 wk, blood samples were taken, and skin hydration (inner forearms and cheek) and melanin content, elasticity, and sebum content (cheek only) were measured. Skin hydration at the inner forearm was higher at wk 4 than at wk 0 in both groups. Sebum content in cheek rose significantly after intervention in the H61-fermented milk group, but not the conventional yogurt group. Other skin parameters did not differ in either group. Serum analysis showed that total protein concentration and platelet count were elevated and reactive oxygen species decreased in both groups after the intervention. Although H61-fermented milk and conventional yogurt had similar effects on skin status and some blood characteristics of participants, an increase of sebum content in cheek is preferable to H61-fermented milk. As skin lipids contribute to maintaining the skin barrier, H61-fermented milk would provide beneficial effects on skin for young women.     

Visible skin colouration predicts perception of male facial age, health and attractiveness

Although there is evidence that perception of facial age, health and attractiveness is informed by shape characteristics as well as by visible skin condition, studies on the latter have focused almost exclusively on female skin. Recent research, however, suggests that a decrease in skin colour homogeneity leads to older, less healthy and less attractive ratings of facial skin in both women and men. Here, we elaborate on the significance of the homogeneity of visible skin colouration in men by testing the hypothesis that perception of age, health and attractiveness of (non-contextual) digitally isolated fields of cheek skin only can predict that of whole facial images. Facial digital images of 160 British men (all Caucasian) aged between 10 and 70 were blind-rated for age, health and attractiveness by a total of 147 men and 154 women (mean age = 22.95, SD = 4.26), and these ratings were related to those of corresponding images of cheek skin reported by Fink et al. (J. Eur. Acad. Dermatol. Venereol. in press). Linear regression analysis showed that age, health and attractiveness perception of men's faces could be predicted by the ratings of cheek skin only, such that older men were viewed as older, less healthy and less attractive. This result underlines once again the potent signalling role of skin in its own right, independent of shape or other factors and suggests strongly that visible skin condition, and skin colour homogeneity in particular, plays a significant role in the perception of men's faces.     

Scientific characterization of subclinical skin changes by noninvasive biophysical methods for development of more efficacious skincare products

In 1966, after finishing only my first year of a residency program, I went to the US to study for 2.5 years with Dr Albert M. Kligman the analysis of functional properties of various skin changes in vivo using aged skin, various types of dermatitis and topically applied steroid-induced atrophy as experimental models. Ten years later, I luckily found that measurements of high frequency conductance and capacitance of the skin enable us to evaluate the skin surface hydration state that determines the softness and smoothness of the skin and in particular to detect even subtle skin changes induced by changes in our environmental or by the application of skincare products and cosmetics. Employing such noninvasive biophysical instruments, I have analyzed the functional properties of normal and abnormal skin changes including subclinical skin changes such as atopic xerosis, senile xerosis, scars and effects of various topical and systemic agents. From these studies it became apparent that as long as a certain level of barrier function was retained skin surface hydration is a more important factor for enjoying a good quality of life. We also succeeded in confirming the effect of corneotherapy, the term so pertinently suggested by Dr Kligman for the beneficial effects of skincare products. We could show that their daily application definitely improves the condition of subclinical skin problems. Further progress in such instrumental analysis of skin properties will greatly aid us in the future in selecting a more desirable skincare product on an individual basis.     

The alkaline pH-adapted skin barrier is disrupted severely by SLS-induced irritation

The pH of the healthy skin is 5.5 and maintained by many regulatory mechanisms. The pH of the skin care product we use on a daily basis can have an influence on the skin properties. To investigate how the physical properties of skin change after the alkaline or acidic pH of the skin care products are applied on the skin for a long term, we adjusted the pH of the skin care products to 3, 5 and 8 (A, B, C), with glycolic acid and triethanolamine. For 5 weeks the skin care products were applied on 20 healthy subjects' ventral forearm and the skin physical properties were measured. After 5 weeks, skin responses to the external stress of 1% (w/v) SLS (sodium lauryl sulphate) irritation and erythema by UV were measured. Skin colour and skin UV response were not altered by the pH. However, on the C-applied site (pH 8) the transepidermal water loss of stratum corneum (SC) increased significantly, the water content increased and desquamation decreased, respectively, and the SLS significantly impaired the skin barrier in comparison with other sites. The alkaline skin care product impaired the skin barrier after repeated application over 5-week period and the skin barrier was disrupted severely by 1% SLS exposure because SC was already impaired by alkaline pH and sensitive to external stress. This suggests that the pH of daily skin care products is very important for skin barrier homeostasis.     

Increased basal transepidermal water loss leads to elevation of some but not all stratum corneum serine proteases

There are indications of elevation of some inflammatory serine proteases in barrier damaged skin (e.g. plasmin and urokinase). Moreover, many other serine protease activities are present such as desquamatory enzymes as well as a newly detected tryptase‐like serine protease. However, the activities of these proteases have never been correlated with stratum corneum (SC) barrier function. The activity of extractable key serine proteases (SC trypsin‐like kallikreins, SC chymotrypsin‐like kallikreins, SC tryptase‐like serine protease, urokinase and plasmin) was measured from the outermost layers of SC obtained from facial tape strippings in clinically normal subjects. The protein content of the tape strippings was quantified by absorption measurements with the novel infrared densitometer SquameScan^TM 850A and the protease activities by the use of fluorogenic peptide substrates. SC barrier function, SC hydration and skin surface pH were measured using AquaFlux^TM, NOVA dermal phase meter and Skin‐pH‐Meter^®, respectively. As expected, SC hydration was reduced with increased transepidermal water loss (TEWL) values indicative of barrier impairment. Surprisingly, SC chymotrypsin‐like activity showed no correlation with hydration or TEWL, whereas all other enzymes positively correlated with impaired barrier function and some were statistically significant: SC trypsin‐like kallikreins (R² = 0.66, P < 0.01), SC tryptase‐like enzyme (R² = 0.95, P < 0.001), plasmin (R² = 0.86, P < 0.001) and urokinase (R² = 0.50, P < 0.05). All enzymes except urokinase also negatively correlated with SC hydration. Elevated levels of SC serine proteases have been associated with some dermatological disorders, such as atopic dermatitis, psoriasis and rosacea but these results indicate that these enzymes are also elevated with milder forms of barrier disruption, which is not clinically evident as irritated skin. As these proteases are elevated in the SC, they will also be elevated in the epidermis where they can be involved in neurogenic inflammation and epidermal barrier impairment via activation of the protease‐activated receptors. These results highlight the need for using serine protease inhibitors especially for urokinase and plasmin, SC tryptase‐like serine protease and possibly SC trypsin‐like kallikreins even in milder forms of barrier damage.