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Staphylococcus aureus colonization is thought to contribute to the pathophysiology of atopic dermatitis (AD). AD patients exhibit reduced levels of cutaneous antimicrobial peptides (AMPs), which may explain their increased susceptibility to infections. Using an in vitro reconstructed human epidermis (RHE) model, we sought to determine whether topical application of a non-replicating probiotic, heat-treated Lactobacillus johnsonii NCC 533 (HT La1), could inhibit S. aureus adhesion to skin and boost cutaneous innate immunity. We found that application of HT La1 suspension to RHE samples reduced the binding of radiolabelled S. aureus by up to 74%. To investigate a potential effect of HT La1 on innate immunity, we analysed the expression of nine AMP genes, including those encoding beta defensins and S100 proteins, following topical application of HT La1 in suspension or in a daily moisturizer lotion. Analysed genes were induced by up to fourfold in a dose-dependent manner by HT La1 in suspension and by up to 2.4-fold by HT La1 in the moisturizer lotion. Finally, using ELISA and immunohistochemical detection, we evaluated the expression and secretion of the AMPs hBD-2 and psoriasin and determined that both proteins were induced by topical HT La1, particularly in the stratum corneum of the RHE. These findings demonstrate that a topically applied, non-replicating probiotic can modulate endogenous AMP expression and inhibit binding of S. aureus to an RHE model in vitro. Moreover, they suggest that a topical formulation containing HT La1 could benefit atopic skin by enhancing cutaneous innate immunity and reducing S. aureus colonization., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Androgens have profound effects on the physiology of the sebaceous gland. Using the hamster ear sebaceous gland model, we performed a detailed kinetic study to clarify the mechanism of androgen action on sebaceous gland function. We demonstrated that the growth of sebaceous glands observed after androgen treatment was due to both an increase in sebocyte proliferation and a parallel induction of sebocyte terminal differentiation, as evidenced by the induction of the synthesis of specific sebaceous lipids such as cholesterol esters, triglycerides, and squalene. Accordingly, the effect of androgen treatment on the mRNA expression of several key enzymes involved in the synthesis of sebaceous lipids has been studied using semi-quantitative RT-PCR. Up-regulation by androgens of mRNA expression of HMG coenzyme A synthase and reductase, acetyl coenzyme A carboxylase (ACC), glycerol 3-phosphate acyl transferase (GPAT), and FAR-17c (stearoyl coenzyme A desaturase homologous), was demonstrated. Because sterol-response element(s) (SREs) are known to be present in the promoters of these genes, we analyzed the expression by RT-PCR and the activation of the transcription factor sterol regulatory element binding protein (SREBP) using immunoblotting experiments. Our results showed that SREBP-1 was up-regulated and rapidly activated after androgen treatment. Altogether, these results demonstrate for the first time that in sebaceous glands, in vivo, androgen regulates the synthesis of sebum lipids through the SREBP pathway.