Interleukin-6-induced inhibition of multiple myeloma cell apoptosis: Support for the hypothesis that protection is mediated via inhibition of the JNK/SAPK pathway

被引:89
作者
Xu, FH
Sharma, S
Gardner, A
Tu, YP
Raitano, A
Sawyers, C
Lichtenstein, A
机构
[1] Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA USA
[2] W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA USA
[3] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA
关键词
D O I
10.1182/blood.V92.1.241.413k28_241_251
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma cells from apoptosis induced by anti-fas antibodies and dexamethasone was studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle distribution or activation of RAF-1 or ERK in dexamethasone or anti-fas-treated 8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability correlated with an inhibition of dexamethasone- and anti-fas-induced activation of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also inhibited c-jun function in 8226 cells via introduction of a mutant dominant negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone-induced apoptosis, These results support the notion that IL-6 protects MM cells against anti-fas through its inhibitory effects on JNK/c-jun but indicate protection against dexamethasone occurs through separate, yet unknown pathways. (C) 1998 by The American Society of Hematology.
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页码:241 / 251
页数:11
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