Ultraviolet light and 8-methoxypsoralen inhibit expression of endothelial adhesion molecules.

Abstract

Having previously found that treating small areas of synovitis within the knees of patients with rheumatoid arthritis (RA) with 8-methoxypsoralen (8-MOP) and laser-derived ultraviolet A (PUVA) resulted in decreases in adhesion molecule expression, we sought to determine the effect of PUVA on expression of vascular cellular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and E-selection by human umbilical vein endothelial cells (HUVEC). Expression of VCAM-1, ICAM-1, and E-selectin on the surface of HUVEC was measured using specific antibodies and flow cytometry or a fluorescence plate reader, following treatment of cells with 8-MOP and UVA, before and after tumor necrosis factor (TNF) stimulation. PUVA led to significant dose dependent decreases in the expression of VCAM-1 and E-selectin that had been induced with TNF before PUVA treatment. Pretreatment with PUVA was also able to prevent subsequent TNF induction of VCAM-1 expression. TNF-induced ICAM-1 expression was not decreased by PUVA, however, and pretreatment only partially decreased ICAM-1 expression. The in vivo effects of PUVA may be explained, in part, by down regulation of adhesion molecule expression. The relative resistance of ICAM-1 to PUVA suggests some specificity to the effect on adhesion molecule expression.