Tumor necrosis factor-α induces adhesion molecule expression through the sphingosine kinase pathway

被引:353
作者
Xia, P
Gamble, JR
Rye, KA
Wang, LJ
Hii, CST
Cockerill, P
Khew-Goodall, Y
Bert, AG
Barter, PJ
Vadas, MA [1 ]
机构
[1] Inst Med & Vet Sci, Div Human Immunol, Hanson Ctr Canc Res, Adelaide, SA 5000, Australia
[2] Inst Med & Vet Sci, Dept Lipid Res, Hanson Ctr Canc Res, Adelaide, SA 5000, Australia
[3] Univ Adelaide, Adelaide, SA 5000, Australia
[4] Womens & Childrens Hosp, Dept Immunol, Adelaide, SA 5000, Australia
关键词
D O I
10.1073/pnas.95.24.14196
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The signaling pathways that couple tumor necrosis factor-alpha (TNF alpha) receptors to functional, especially inflammatory, responses have remained elusive. We report here that TNF alpha induces endothelial cell activation, as measured by the expression of adhesion protein E-selectin and vascular adhesion molecule-1, through the sphingosine kinase (SKase) signaling pathway. Treatment of human umbilical vein endothelial cells with TNF alpha resulted in a rapid SKase activation and sphingosine l-phosphate (S1P) generation. SLP, but not ceramide or sphingosine, was a potent dose-dependent stimulator of adhesion protein expression. S1P was able to mimic the effect of TNF alpha on endothelial cells leading to extracellular signal-regulated kinases and NF-KB activation, whereas ceramide or sphingosine was not. Furthermore, N,N-dimethylsphingosine, an inhibitor of SKase, profoundly inhibited TNF alpha-induced extracellular signal-regulated kinases and NF-KB activation and adhesion protein expression. Thus we demonstrate that the SKase pathway through the generation of SLP is critically involved in mediating TNF alpha-induced endothelial cell activation.
引用
收藏
页码:14196 / 14201
页数:6
相关论文
共 35 条
[1]   FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase [J].
AdamKlages, S ;
Adam, D ;
Wiegmann, K ;
Struve, S ;
Kolanus, W ;
SchneiderMergener, J ;
Kronke, M .
CELL, 1996, 86 (06) :937-947
[2]   (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol as an inhibitor of ceramidase [J].
Bielawska, A ;
Greenberg, MS ;
Perry, D ;
Jayadev, S ;
Shayman, JA ;
McKay, C ;
Hannun, YA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (21) :12646-12654
[3]  
CARLOS TM, 1994, BLOOD, V84, P2068
[4]   Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95 [J].
Chinnaiyan, AM ;
ORourke, K ;
Yu, GL ;
Lyons, RH ;
Garg, M ;
Duan, DR ;
Xing, L ;
Gentz, R ;
Ni, J ;
Dixit, VM .
SCIENCE, 1996, 274 (5289) :990-992
[5]  
Choi OH, 1996, NATURE, V380, P634
[6]   TRANSCRIPTIONAL REGULATION OF ENDOTHELIAL-CELL ADHESION MOLECULES - NF-KAPPA-B AND CYTOKINE-INDUCIBLE ENHANCERS [J].
COLLINS, T ;
READ, MA ;
NEISH, AS ;
WHITLEY, MZ ;
THANOS, D ;
MANIATIS, T .
FASEB JOURNAL, 1995, 9 (10) :899-909
[7]   Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate [J].
Cuvillier, O ;
Pirianov, G ;
Kleuser, B ;
Vanek, PG ;
Coso, OA ;
Gutkind, JS ;
Spiegel, S .
NATURE, 1996, 381 (6585) :800-803
[8]  
Ferrell JE, 1996, CURR TOP DEV BIOL, V33, P1, DOI 10.1016/S0070-2153(08)60336-1
[9]  
GAMBLE JR, 1993, J IMMUNOL, V150, P4494
[10]   INTRACELLULAR CALCIUM RELEASE MEDIATED BY SPHINGOSINE DERIVATIVES GENERATED IN CELLS [J].
GHOSH, TK ;
BIAN, J ;
GILL, DL .
SCIENCE, 1990, 248 (4963) :1653-1656