ULTRAVIOLET-RADIATION ACTIVATES THE HUMAN ELASTIN PROMOTER IN TRANSGENIC MICE - A NOVEL IN-VIVO AND IN-VITRO MODEL OF CUTANEOUS PHOTOAGING

The major alteration in photoaged skin is the deposition of massive am ounts of abnormal elastic material, termed solar elastosis. In previou s work, it has been shown that solar elastosis is accompanied by incre ased abundance of elastin and fibrillin mRNAs and upregulation of elas tin promoter activity. Using a transgenic mouse line, which expresses the human elastin promoter, linked to a chloramphenicol acetyltransfer ase reporter gene, in a tissue-specific and developmentally regulated manner, we investigated the effects of ultraviolet A radiation and ult raviolet B radiation on human elastin promoter activity in vivo and in vitro. Irradiation of mice with a single dose of ultraviolet B radiat ion (491.4 mJ/cm(2)) resulted in an increase up to 8.5-fold in promote r activity, whereas a more modest increase of 1.8-fold was measured wi th ultraviolet A radiation (38.2 J/cm(2)). In addition, in vitro studi es revealed over a thirtyfold increase in elastin promoter activity in response to ultraviolet B radiation (5.5 mJ/cm(2)), whereas no change was measured in response to ultraviolet A radiation (2.2 J/cm(2)). Th ese results confirm the role of ultraviolet B radiation in elastin pro moter activation in photoaging, and identify ultraviolet A radiation a s a contributing factor. This system should serve as a useful in vivo and in vitro model to study cutaneous photoaging, and for testing comp ounds that may protect against cutaneous photodamage.