Cytokines as suppressors of apoptosis

被引:36
作者
Lotem, J [1 ]
Sachs, L [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
关键词
apoptosis suppression; cancer therapy; cytokines; genes and pathways of apoptosis; hematopoietic cells; leukemia; neurons;
D O I
10.1023/A:1009614723237
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Many cytokines have been isolated by their ability to induce growth and have been called growth factors. But these cytokines are also essential to induce cell viability, and cell viability and growth can be separately regulated. Using as examples myeloid hematopoietic cells, lymphocytes and neuronal cells, in vitro and in vivo studies have shown the role of cytokines in inducing viability of different cell types during development to mature cells. Some cytokines can act on more than one cell type. Cytokines induce viability of normal and cancer cells by suppressing the apoptotic machinery activated by wild-type p53, or by cytotoxic agents including irradiation and compounds used in cancer chemotherapy. Cytokines can be used to decrease apoptosis in normal cells and inhibition of cytokine activity may improve cancer therapy by enhancing apoptosis in cancer cells. The apoptosis suppressing function of cytokines is mediated by changing the balance in the activity of apoptosis inducing and suppressing genes. Apoptosis suppression is upstream of caspase activation in the apoptotic process. Cytokines can suppress multiple pathways leading to apoptosis, only some of which were suppressed by other agents such as some antioxidants, Ca2+-mobilizing compounds and protease inhibitors.
引用
收藏
页码:187 / 196
页数:10
相关论文
共 139 条
[1]  
ABRAHAMSON JLA, 1995, MOL CELL BIOL, V15, P6953
[2]   The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[3]   Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice [J].
Akashi, K ;
Kondo, M ;
vonFreedenJeffry, U ;
Murray, R ;
Weissman, IL .
CELL, 1997, 89 (07) :1033-1041
[4]   GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo [J].
Arenas, E ;
Trupp, M ;
Akerud, P ;
Ibanez, CF .
NEURON, 1995, 15 (06) :1465-1473
[5]  
ARENDS MJ, 1991, INT REV EXP PATHOL, V32, P223
[6]   Death receptors: Signaling and modulation [J].
Ashkenazi, A ;
Dixit, VM .
SCIENCE, 1998, 281 (5381) :1305-1308
[7]   BIOLOGIC EFFECTS OF ANTI-INTERLEUKIN-6 MURINE MONOCLONAL-ANTIBODY IN ADVANCED MULTIPLE-MYELOMA [J].
BATAILLE, R ;
BARLOGIE, B ;
LU, ZY ;
ROSSI, JF ;
LAVABREBERTRAND, T ;
BECK, T ;
WIJDENES, J ;
BROCHIER, J ;
KLEIN, B .
BLOOD, 1995, 86 (02) :685-691
[8]   Defects in regulation of apoptosis in caspase-2-deficient mice [J].
Bergeron, L ;
Perez, GI ;
Macdonald, G ;
Shi, LF ;
Sun, Y ;
Jurisicova, A ;
Varmuza, S ;
Latham, KE ;
Flaws, JA ;
Salter, JCM ;
Hara, H ;
Moskowitz, MA ;
Li, E ;
Greenberg, A ;
Tilly, JL ;
Yuan, JY .
GENES & DEVELOPMENT, 1998, 12 (09) :1304-1314
[9]   INTERLEUKIN-6 IS REQUIRED IN-VIVO FOR THE REGULATION OF STEM-CELLS AND COMMITTED PROGENITORS OF THE HEMATOPOIETIC SYSTEM [J].
BERNAD, A ;
KOPF, M ;
KULBACKI, R ;
WEICH, N ;
KOEHLER, G ;
GUTIERREZRAMOS, JC .
IMMUNITY, 1994, 1 (09) :725-731
[10]   INOSITOL TRISPHOSPHATE AND CALCIUM SIGNALING [J].
BERRIDGE, MJ .
NATURE, 1993, 361 (6410) :315-325