Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells
Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells
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DOI：
10.1182/blood.v89.1.227.227_227_234
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发表时间：
1997-01-01
期刊：
影响因子：
20.3
通讯作者：
Anderson, KC
中科院分区：
文献类型：
--
作者：
Chauhan, D;Kharbanda, S;Anderson, KC
Fas属于转导细胞凋亡信号的1型膜蛋白家族。在目前的研究中，我们在RPMI-8226和IM-9多发性骨髓瘤(MM)来源的细胞系以及患者浆细胞白血病细胞中研究了Fas诱导凋亡的信号转导过程。抗PAS(7C11)单抗(Moab)诱导细胞凋亡，核小体DNA片段化和碘化丙啶染色证实，并与c-jun早期反应基因表达增加有关。我们还发现，抗Fas单抗处理与应激激活蛋白激酶(SAPK)和p38丝裂原活化蛋白激酶(MAPK)的激活有关，但没有观察到细胞外信号调节蛋白激酶(ERK1和ERK2)活性的明显增加。由于白介素6(IL-6)是MM细胞的生长因子，可抑制地塞米松和血清饥饿诱导的细胞凋亡，因此我们检测了IL-6是否影响抗Fas单抗诱导的MM细胞的凋亡及SAPK和p38MAPK的激活。在用抗Fas单抗处理MM细胞之前加入IL-6可显著减少DNA片段化和SAPK的激活，但不改变对p38MAPK活性的诱导。这些结果提示，抗Fas单抗诱导MM细胞的凋亡与SAPK的激活有关，IL-6既可抑制细胞凋亡，又可调节SAPK的活性。(C)1997年由美国血液病学会主办。
Fas belongs to the family of type-1 membrane proteins that transduce apoptotic signals. In the present studies, we characterized signaling during Fas-induced apoptosis in RPMI-8226 and IM-9 multiple myeloma (MM) derived cell lines as well as patient plasma cell leukemia cells. Treatment with anti-pas (7C11) monoclonal antibody (MoAb) induced apoptosis, evidenced by internucleosomal DNA fragmentation and propidium iodide staining, and was associated with increased expression of c-jun early response gene. We also show that anti-fas MoAb treatment is associated with activation of stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (MAPK); however, no detectable increase in extracellular signal-regulated kinases (ERK1 and ERK2) activity was observed. Because interleukin-6 (IL-6) is a growth factor for MM cells and inhibits apoptosis induced by dexamethasone and serum starvation, we examined whether IL-6 affects anti-fas MoAb-induced apoptosis and activation of SAPK or p38 MAPK in MM cells. Culture of MM cells with IL-6 before treatment with anti-fas MoAb significantly reduced both DNA fragmentation and activation of SAPK, without altering induction of p38 MAPK activity. These results therefore suggest that anti-fas MoAb-induced apoptosis in MM cells is associated with activation of SAPK, and that IL-6 may both inhibit apoptosis and modulate SAPK activity. (C) 1997 by The American Society of Hematology.