ALL-TRANS-RETINOIC ACID DOWN-REGULATES ELASTIN PROMOTER ACTIVITY ELEVATED BY ULTRAVIOLET-B IRRADIATION IN CULTURED SKIN FIBROBLASTS

Topical tretinoin therapy produces clinical improvements in the fine w rinkling of photodamaged skin, possibly by enhancement of collagen syn thesis. A major biochemically and histologically detectable change in photodamaged skin is the accumulation of abnormal elastic fibers (elas totic material). However, little is known about the effects of retinoi c acid and ultraviolet B (UVB) on elastin gene expression. Consequentl y, we examined the effects of all-tr ans-retinoic acid (t-RA) and UVB on elastin gene expression in cultured human skin fibroblasts in vitro . Elastin mRNA gene expression was up-regulated in response to UVB by approximate to 3-fold, in a dose dependent manner, between 3 and 10 mJ /cm(2) doses. Similar results were obtained by chloramphenicol acetylt ransferase assay, in which a maximal promoter activation more than 5.4 -fold that in nonirradiated controls occurred after a single dose of 2 0 mJ/cm(2). Also, t-RA inhibited the increase in elastin mRNA level fo llowing a single exposure to UVB by approximately 16%, and the increas e in promotor activity by about 65%. The inhibitory effect of t-RA on elastin induced by UVB was also demonstrated by indirect immunofluores cence studies. Taken together, t-RA down-regulated human elastin gene expression elevated by a single exposure to UVB at transcriptional and possibly protein levels. These results suggest that the anti-photoagi ng effect of t-RA may be related, at least in part, to down-regulation of elastin gene expression elevated by UVB. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.