Topically applied lactic acid increases spontaneous secretion of vascular endothelial growth factor by human reconstructed epidermis

Background: Alpha-hydroxy acids (AHAs) are widely used for the treatment of hyperkeratotic skin disorders and photodamaged skin. Objectives: To investigate the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes (KCs) of human reconstructed epidermis. Methods: Creams containing 1.5%, 3% or 5% LA or vehicle controls were topically applied on to human epidermal equivalents (EEs). After 24 h, EEs were analysed for morphology and for the presence of apoptotic cells. Secretion of vascular endothelial growth factor (VEGF), angiogenin (ANG) and interleukin (IL)-8 was measured in the supernatants by enzyme-linked immunosorbent assay. Results: LA led to a concentration-dependent increase in apoptotic cells as determined by cell morphology and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling. VEGF secretion was increased 2.5- and 2.8-fold (P < 0.05) over vehicle control after treatment with 1.5% and 3% LA, respectively. No significant increase in VEGF secretion was detected with 5% LA. In contrast to VEGF, secretion of ANG was decreased by LA in a concentration-dependent manner (0.5-fold for 5% LA; P < 0.01). No significant changes in IL-8 secretion were found with any of the concentrations tested. Conclusions: Our data demonstrate that the topical application of AHAs modulates the secretion of cytokines by KCs. Regulation of KC-derived growth factors and cytokines by AHAs might represent a mechanism contributing to their therapeutic effects in disorders such as photoageing.