The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function. We observed a strikingly broad range of claudin-1 levels with stable TJ and overall skin barrier function in healthy and non-lesional skin. However, a significant decrease in TJ barrier function was detected in lesional AD skin where claudin-1 levels were further reduced. Investigations on reconstructed human epidermis expressing different levels of claudin-1 revealed that claudin-1 levels correlated with insideout and outside-in barrier function, with a higher coherence for smaller molecular tracers. Claudin-1 decrease induced keratinocyte-autonomous IL-1β expression and fostered inflammatory epidermal responses to non-pathogenic Staphylococci. In conclusion, claudin-1 decrease beyond a threshold level results in TJ and epidermal barrier function impairment and induces inflammation in human epidermis. Increasing claudin-1 levels might improve barrier function and decrease inflammation and therefore be a target for AD treatment. Tight junctions (TJs) are an important component of the complex epidermal barrier system. They are localized in the stratum granulosum (SG) of the epidermis and provide mechanical barrier function to ions and solutes of different molecular sizes 1-4. The transmembrane protein claudin-1 (Cldn-1) is a major component of TJs 5. It is also found outside of TJs in basal and suprabasal layers of the epidermis 2,5. Mice with a complete Cldn-1 knockout (KO) die at the first day of birth due to increased transepidermal water loss (TEWL) 5. They develop TJs leaky to a molecular tracer (Biotin-556) 5 , and a highly water permeable stratum corneum (SC) 6. Human subjects lacking Cldn-1 suffer from the Neonatal Ichthyosis-Sclerosing Cholangitis (NISCH) syndrome which includes an ichthyosiform skin phenotype 7. An archetypical disease of epidermal barrier dysfunction is atopic dermatitis (AD) 8. Cldn-1 single nucleotide polymorphisms were linked to AD in some cohorts 9-11 , but not in others 11,12. Using immunostaining-intensity measurements and western blot analyses, reduced Cldn-1 levels were found in lesional AD skin 13-16. For non-lesional skin, divergent observations were described. Some authors found decreased mRNA and immunointensity levels 10 , while others observed no alteration of Cldn-1 immunointensity and western-blot levels 14,16 .

(2017) A new topical panthenol-containing emollient: Results from two randomized controlled studies assessing its skin moisturization and barrier restoration potential, and the effect on skin microflora, Journal of Dermatological Treatment, 28:2, 173-180, DOI: 10.1080/09546634.2016 Purpose: Two randomized, intra-individual comparison studies were performed in healthy subjects to evaluate the skin moisturization and barrier restoration potential of a new topical panthenol-containing emollient (NTP-CE) (Study 1), and its effect on skin microflora (Study 2). Methods: In Study 1 (N ¼ 23), two skin areas, one challenged with 0.5% sodium dodecyl sulfate (SDS) solution and one unchallenged, were treated with NTP-CE for 3 weeks. Transepidermal water loss (TEWL), skin hydration, and intercellular lipid lamellae (ICLL) organization were measured at regular intervals during the study. In Study 2 (N ¼ 20), quantitative bacterial cultures were obtained over 6 h from a skin area undergoing wash stress with 10% SDS with subsequent single application of NTP-CE. Results: In Study 1, mean AUC for TEWL reduction from baseline was more pronounced with NTP-CE compared with control (À168.36 vs. À123.38 g/m 2 /h, p ¼ 0.023). NTP-CE use was also associated with statistically significant improvements in stratum corneum hydration and an increase in mean ICLL length from baseline (day 22: 120.61 vs. 35.85 nm/1000 nm 2 , p < 0.001). In Study 2, NTP-CE use had no negative impact on bacterial viability. Conclusions: NTP-CE use has favorable and lasting effects on barrier function and repair as well as skin hydration without negatively influencing bacterial viability. ARTICLE HISTORY

The investigated Ec. extract shows great potential in alleviating cutaneous symptoms of AE, and by exerting remarkable anti-inflammatory actions and restoring the epidermal lipid barrier, it will be very likely a well-tolerated, powerful novel ingredient for the adjuvant therapy of AE.

In summary, topical application of a pH 4.0 product containing plant oils improves epidermal barrier formation and SC lipid ordering and ratio in aged dry skin.

Patients with atopic dermatitis (AD) have an epidermal barrier dysfunction, which allows invasion of allergens to occur. Stratum corneum skin barrier is formed by corneocytes and extracellular lipids extruded from the epidermal lamellar bodies. In a controlled, randomized, double-blinded, right-left comparison study we investigated the effect of pimecrolimus (PIM) cream compared with triamcinolone acetonide cream (TA) on the skin barrier in 15 patients with symmetrical elbow lesions of AD. In punch biopsies, before and after treatment, skin lipid bilayer and lamellar body structure were examined by transmission electron microscopy (TEM). Partial Eczema Area and Severity Index (pEASi), stratum corneum hydration, and transepidermal water loss (TEWL) were monitored on days 1, 8 and 22. The pEASi was significantly more improved with TA compared with PIM, whereas stratum corneum hydration was slightly more improved after treatment with PIM. The TEM revealed a strong reduction in lamellar bodies in lesional skin of AD; only 32% of the lamellar bodies were normal. A significantly higher number of normal lamellar bodies was found after 3 weeks of treatment with PIM (58%; p < 0.005). An increase in lamellar bodies also occurred with TA treatment (46%; p < 0.05); however, significantly less than with PIM (p < 0.05). Clinical score and TEWL were more improved after treatment with TA, whereas the lamellar bodies were more normal after treatment with PIM.