Sphingosylphosphorylcholine is a potent inducer of intercellular adhesion molecule-1 expression in human keratinocytes

We recently reported that the epidermis of patients with atopic dermatitis contains an abnormally expressed sphingomyelin deacylase that yields a larg e amount of sphingosylphosphorylcholine (SPC) rather than ceramide, In this study, we characterize inflammatory roles of newly discovered chemicals in the epidermis by elucidating biologic effects of SPC on intercellular adhe sion molecules-1 (ICAM-1) expression by human keratinocytes in culture in c omparison with other sphingolipids. Using fluorescence-activated cell sorte r analysis, we found that SPC treatment at concentrations of 10-20 mu M sig nificantly enhanced the expression of ICAM-1 by cultured human keratinocyte s in a dose-dependent manner after incubation for 15-24 h, and, using north ern blot analysis, that this was accompanied by increased expression of ICA M-1 mRNA within 4 h of incubation. Transforming necrosis factor-alpha (TNF- alpha) levels in the medium of keratinocytes treated at a 10 mu M concentra tion of SPC were significantly increased by 200%. Furthermore, the SPC-indu ced ICAM-1 expression was partially abolished by the concomitant addition o f anti-TNF-alpha, suggesting a partial autocrine involvement of TNF-alpha i n ICAM-1 expression, Assay of mitogen-activated protein kinase revealed tha t 10 mu M SPC induced a rapid activation of mitogen-activated protein kinas e in human keratinocytes, including an increase in its phosphorylation with in 5 min, which then declined to the baseline control level after 30 min. I n contrast, sphingomyelin or sphingosine had no significant potential to ac tivate mitogen-activated protein kinase at the same concentration. These fi ndings suggest that SPC plays an important role in the inflammatory process of epidermis in skin diseases, such as atopic dermatitis, with high expres sion of sphingomyelin deacylase.