426 Effect of L-4-thiazolylalanine on skin barrier strength

Abstract

Skin barrier properties are critical for maintaining epidermal water content, protecting from environmental factors, and providing first line of defense against pathogens. In this study, the effect of a non-proteinogenic amino acid, L-4-Thiazolylalanine (L4), on this important aspect of skin health was evaluated by in vitro and in vivo biomarkers. 3D human skin models were treated with 0.3% L4. After 48h, RNA samples were collected and gene expression analyzed. Significant increase in the expression of ALOXE3 (protein eLOX-3) vs. vehicle (VEH) (+27%) was measured. eLOX-3 is a member of the lipoxygenase family required in the epidermis for the covalent linkage of ceramides to proteins of the cornified envelope, an important step in establishing skin barrier function. To further evaluate skin barrier integrity, trans-epithelial electrical resistance (TEER) was measured in the 3D tissues at basal level as well as upon barrier disruption. TEER is a quantitative method that allows barrier strength evaluation. TEER values are highly related to the tight junction barrier function and decrease upon disruption induced by calcium depletion. L4 treatment induced a significant increase in TEER vs. vehicle and protected from low calcium-induced barrier decrease. Clinically, skin treated with L4 for 4 weeks had better barrier integrity vs. vehicle control. This was shown via instrumentation and evaluation of biomarkers in skin samples collected via tape stripping. A fluorescence-based assay was used to quantify the enzymatic activity of 12R-LOX, another lipoxygenase critical for maturation of skin barrier ceramides. Significant increase in 12R-LOX activity was measured after L4 treatment vs. vehicle (+31%) with a stronger effect in subjects 40 years-old and older (+45%). In conclusion, L4 led to modulation of in vitro and in vivo biomarkers critical for skin barrier strength, making it desirable ingredient for topical treatments.