Differential TNF-signaling in chronic inflammatory disorders

被引:116
作者
Holtmann, MH [1 ]
Neurath, MF [1 ]
机构
[1] Johannes Gutenberg Univ Mainz, Dept Med, D-55131 Mainz, Germany
关键词
TNF-alpha; TNF-R2; signal transduction; inflammatory disorders;
D O I
10.2174/1566524043360636
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
TNF-alpha is a pleiotropic cytokine with strong proinflammatory and immunomodulatory properties. TNF-alpha plays a critical role in many acute or chronic inflammatory diseases and anti-TNF-strategies have proven to be clinically effective. Two TNF-specific cell surface receptors TNF-R1 and TNF-R2 have been identified and the function of these receptors and the downstream intracellular signal transduction pathways have been extensively studied in vitro. For a long time TNF-R1 was considered to be the predominant mediator of TNF-signaling, whereas TNF-R2 was ascribed only auxilliary function. However, there is increasing clinical and experimental evidence for an important independent role of p80 signaling in chronic inflammatory conditions. It is conceivable that the multiple TNF-mediated chronic inflammatory disorders differ in terms of the ligand form (soluble TNF-alpha versus membrane bound TNF-alpha), the receptor (TNF-R1 versus TNF-R2) and the downstream signaling cascades utilized. The elucidation of the specific characteristics of TNF-signaling in distinct inflammatory disorders will lead to a better understanding ot the pathogenesis of these diseases and will be the basis for the development of more specific and more efficient therapeutic approaches.
引用
收藏
页码:439 / 444
页数:6
相关论文
共 77 条
[61]   THE MOUSE-HUMAN CHIMERIC MONOCLONAL-ANTIBODY CA2 NEUTRALIZES TNF IN-VITRO AND PROTECTS TRANSGENIC MICE FROM CACHEXIA AND TNF LETHALITY IN-VIVO [J].
SIEGEL, SA ;
SHEALY, DJ ;
NAKADA, MT ;
LE, JM ;
WOLFE, DS ;
PROBERT, L ;
KOLLIAS, G ;
GHRAYEB, J ;
VILCEK, J ;
DADDONA, PE .
CYTOKINE, 1995, 7 (01) :15-25
[62]   RIP - A NOVEL PROTEIN CONTAINING A DEATH DOMAIN THAT INTERACTS WITH FAS/APO-1 (CD95) IN YEAST AND CAUSES CELL-DEATH [J].
STANGER, BZ ;
LEDER, P ;
LEE, TH ;
KIM, E ;
SEED, B .
CELL, 1995, 81 (04) :513-523
[63]   Human pro-tumor necrosis factor is a homotrimer [J].
Tang, P ;
Hung, MC ;
Klostergaard, J .
BIOCHEMISTRY, 1996, 35 (25) :8216-8225
[64]   A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease [J].
Targan, SR ;
Hanauer, SB ;
vanDeventer, SJH ;
Mayer, L ;
Present, DH ;
Braakman, T ;
DeWoody, KL ;
Schaible, TF ;
Rutgeerts, PJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (15) :1029-1035
[65]   Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease [J].
ten Hove, T ;
van Montfrans, C ;
Peppelenbosch, MP ;
van Deventer, SJH .
GUT, 2002, 50 (02) :206-211
[66]   IDENTIFICATION OF A 60-KD TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR AS THE MAJOR SIGNAL TRANSDUCING COMPONENT IN TNF RESPONSES [J].
THOMA, B ;
GRELL, M ;
PFIZENMAIER, K ;
SCHEURICH, P .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (04) :1019-1023
[67]   Caspases: Enemies within [J].
Thornberry, NA ;
Lazebnik, Y .
SCIENCE, 1998, 281 (5381) :1312-1316
[68]   TUMOR-NECROSIS-FACTOR - A PLEIOTROPIC CYTOKINE AND THERAPEUTIC TARGET [J].
TRACEY, KJ ;
CERAMI, A .
ANNUAL REVIEW OF MEDICINE, 1994, 45 :491-503
[69]   TUMOR-NECROSIS-FACTOR, OTHER CYTOKINES AND DISEASE [J].
TRACEY, KJ ;
CERAMI, A .
ANNUAL REVIEW OF CELL BIOLOGY, 1993, 9 :317-343
[70]   FIBRINOLYTIC RESPONSE TO TUMOR-NECROSIS-FACTOR IN HEALTHY-SUBJECTS [J].
VANDERPOLL, T ;
LEVI, M ;
BULLER, HR ;
VANDEVENTER, SJH ;
DEBOER, JP ;
HACK, CE ;
TENCATE, JW .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (03) :729-732