title: N,N,N-trimethylsphingosine inhibits interleukin-1 beta-induced NF-kappa B activation and consequent E-selectin expression in human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: Biomembrane Institute, Seattle, WA 98119, USA.
authors.forename: A
authors.initials: A
authors.lastname: Masamune
authors.forename: S
authors.initials: S
authors.lastname: Hakomori
authors.forename: Y
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D015536:Down-Regulation; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D016328:NF-kappa B; C071600:N,N,N-trimethylsphingosine; D011493:Protein Kinase C; C061800:N,N-dimethylsphingosine; D013110:Sphingosine