SELECTIVE UP-REGULATION OF INTERCELLULAR-ADHESION MOLECULE (ICAM-1) BY ULTRAVIOLET-B IN HUMAN DERMAL MICROVASCULAR ENDOTHELIAL-CELLS

Although a portion of ultraviolet light (UV) penetrates into the dermi s, histologic changes that occur within the dermal microvasculature ha ve largely been attributed to the elaboration of biologic substances, such as interleukin 1 (IL-1), from other constitutive cells of the ski n, as opposed to a direct effect of UV on the endothelial cell. As a p otential model for understanding early molecular events occurring in U V-induced cutaneous inflammation, we have examined the direct effects of UVB, as well as cytokine-positive controls, upon human dermal micro vascular endothelial cells (HDMEC) cell adhesion molecule (CAM) gene e xpression. Cultured HDMEC were exposed to varying dosages of UVB, and examined for cell surface and mRNA expression of the CAMs intercellula r adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCA M-1), and E-selectin (formerly ELAM-1). Following UVB exposure, dose-d ependent increases in baseline cell surface expression of ICAM-1 were demonstrated by fluorescence-activated cell sorter analysis with conco mitant increases in ICAM-1 mRNA, as shown by Northern blot analysis; t here was no induction of either E-selectin or VCAM-1. The UVB-induced ICAM-1 upregulation could not be blocked by antibodies to IL-1 or tumo r necrosis factor alpha (TNF-alpha). In fact, ICAM-1 gene regulatory r egion based CAT reporter gene plasmids, including constructs containin g IL-1- and TNF-alpha-responsive elements, did not display increased C AT expression after transfection into HDMEC followed by UVB exposure, though control cytokine-treated transfectants did. Thus, UVB selective ly upregulates ICAM-1, but not E-selectin or VCAM-1, mRNA and cell sur face expression in HDMEC, and this upregulation is not dependent upon the autologous secretion and activity of either IL-1 or TNF-alpha.