Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells
Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells
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DOI：
10.1038/sj.leu.2402481
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发表时间：
2002-06-01
期刊：
影响因子：
11.4
通讯作者：
Van Ness, B
中科院分区：
文献类型：
--
作者：
Cheung, WC;Van Ness, B
在B细胞发育过程中，白介素6(IL-6)可诱导B淋巴细胞最终成熟为产生抗体的浆细胞。终末分化的B细胞细胞周期停滞和死亡随之而来。相比之下，IL-6作为恶性骨髓瘤浆细胞的生长因子，在某些情况下保护它们免受治疗。在这项研究中，我们研究了两种对IL-6表现出不同反应的细胞株。淋巴母细胞样细胞对IL-6的反应是通过终末分化为产生抗体的浆细胞，细胞周期停止，并经历细胞死亡。持续加入IL-6可诱导STAT3、SHP-2磷酸化的瞬时激活，但不改变bc1-X-L和c-myc的表达。相反，骨髓瘤细胞株ANBL6在IL-6刺激下增殖，这与STAT3激活时间延长和bc1-X-L和c-myc上调有关。有趣的是，在IL-6诱导的CES细胞中检测到gp130相关的SHP-2磷酸化，但在骨髓瘤细胞系中没有检测到。数据显示在这些细胞系中有非常不同的IL-6信号转导和动力学，并且不同的分子事件与淋巴母细胞和骨髓瘤细胞系的细胞命运密切相关。
In B cell development, interleukin-6 (IL-6) induces terminal maturation of B lymphocytes into antibody producing plasma cells. Terminal differentiated B cells cell cycle arrest and death follows. In contrast, IL-6 acts as a growth factor for malignant myeloma plasma cells and in some cases protects them from therapeutic treatment. In this study, we examined two cell lines that show different responses to IL-6. Lymphoblastoid CESS cells respond to IL-6 by terminally differentiating into antibody producing plasma cells, cell cycle arrest, and undergo cell death. Continuous addition of IL-6 to these cells induces transient activation of STAT3, SHP-2 phosphorylation, and does not alter bcl-X-L and c-myc expression. In contrast, the myeloma line ANBL6 proliferates when stimulated with IL-6 and this correlates with prolonged STAT3 activation and up-regulation of bcl-X-L and c-myc. Interestingly, gp130-associated SHP-2 phosphorylation was detected in the IL-6-induced CESS cells but not myeloma cell lines. The data show a very distinct IL-6 signal transduction and kinetics in these cell lines and the distinct molecular events correlate closely to the cell fate of the lymphoblast and myeloma cell lines.