N,N,N-trimethylsphingosine inhibits interleukin-1 beta-induced NF-kappa B activation and consequent E-selectin expression in human umbilical vein endothelial cells.

We examined the effect of N,N,N-trimethylsphingosine (TMS) on the interleukin-1 beta (IL-1 beta)-induced E-selectin expression in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with TMS (0.1-10 microM) resulted in a concentration-dependent inhibition of IL-1 beta-induced E-selectin expression. Sphingosine or N,N-dimethylsphingosine had no effects on the expression. Electrophoretic mobility shift assay revealed that TMS inhibited IL-1 beta-induced NF-kappa B activation, which is essential for E-selectin expression. This inhibitory effect of TMS on IL-1 beta-dependent endothelial cell activation may partly explain the known anti-inflammatory or anti-metastatic effect of TMS in vivo.