Effects of all-trans retinoic acid on UVB-irradiated human skin substitute

Retinoids are frequently used for treatment of photodamaged skin. We wished to find out whether photodamage could be attenuated by applying all-trans retinoic acid (RA) during repetitive irradiation. For this purpose, we used human cutaneous cells and tissue: pure monolayer cultures containing eithe r keratinocytes or fibroblasts, and human skin substitute (SS) containing b oth cell types. All cultures were exposed to 8 mJ/cm(2) of UVB and were imm ediately treated with RA (0, 1.5, or 3 mu M). The irradiation and RA treatm ent protocol was repeated until the cells of the nonirradiated culture had reached confluence. In the irradiated SS, RA preserved the structure (epide rmal stratification and differentiation) and ultrastructure (well-organized intermediate filaments and desmosomes) in a state comparable to that obser ved in non irradiated SS. As well RA maintained secretion of basement membr ane components (laminin and type-IV collagen). Following irradiation, cutan eous cells also displayed more proliferative capacity when SS was treated. In the irradiated monolayer cultures, RA maintained the proliferative capac ity of fibroblasts and decreased their differentiation whereas the opposite effect was seen on keratinocytes. In conclusion, RA clearly helps protect human skin against photodamage induced by repeated exposure to UVB. J. Cell . Physiol. 181:14-23, 1999. (C) 1999 Wiley-Liss, Inc.