We recently reported that the epidermis of patients with
atopic dermatitis contains an abnormally expressed
sphingomyelin deacylase that yields a large 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 adhesion molecules-1 (ICAM-I) expression by human keratinocytes in culture in comparison with other
sphingolipids. Using fluorescence-activated cell sorter analysis, we found that SPC treatment at concentrations of 10-20 microM significantly enhanced the expression of ICAM-I by cultured human keratinocytes in a dose-dependent manner after incubation for 15-24 h, and, using northern blot analysis, that this was accompanied by increased expression of
ICAM-1 mRNA within 4 h of incubation. Transforming
necrosis factor-alpha (
TNF-alpha) levels in the medium of keratinocytes treated at
a 10 microM concentration of SPC were significantly increased by 200%. Furthermore, the SPC-induced
ICAM-1 expression was partially abolished by the concomitant addition of anti-
TNF-alpha, suggesting a partial autocrine involvement of
TNF-alpha in
ICAM-1 expression. Assay of
mitogen-activated protein kinase revealed that 10 microM SPC induced a rapid activation of
mitogen-activated protein kinase in human keratinocytes, including an increase in its phosphorylation within 5 min, which then declined to the baseline control level after 30 min. In contrast,
sphingomyelin or
sphingosine had no significant potential to activate
mitogen-activated protein kinase at the same concentration. These findings suggest that SPC plays an important role in the inflammatory process of epidermis in
skin diseases, such as
atopic dermatitis, with high expression of
sphingomyelin deacylase.