Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression.
Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression.
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DOI：
10.1084/jem.176.5.1319
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发表时间：
1992-11-01
影响因子：
15.3
通讯作者：
SARFATI, M
中科院分区：
文献类型：
--
作者：
DANCESCU, M;RUBIOTRUJILLO, M;BIRON, G;BRON, D;DELESPESSE, G;SARFATI, M
慢性淋巴细胞白血病（B- cll）的特点是缓慢分裂和长寿命的单克隆B细胞在其分化的中间阶段被阻止。我们之前的研究表明，白细胞介素4 （IL-4）不仅抑制而且阻止B-CLL细胞的增殖。我们在此报告IL-4保护B-CLL细胞免于凋亡（程序性细胞死亡[PCD]）。IL-4抑制12例未选择的CLL患者的高纯化B细胞自发和氢化可的松（HC）诱导的PCD，显示出持续的细胞活力和缺乏DNA断裂。IL-1、-2、-3、- 5、-6、-7、肿瘤坏死因子α、转化生长因子β无保护作用。IL-4在体外对细胞凋亡的拯救作用表现为Bcl-2蛋白的表达增加，Bcl-2蛋白是一种直接参与延长体内和体外细胞存活的原癌基因。因此，il -4处理的B-CLL细胞比未刺激的、hc处理的或新鲜的B-CLL细胞表达更多的Bcl-2。此外，一名CLL患者皮下注射IL-4可提高白血病B细胞中Bcl-2蛋白的表达。这些数据可能表明IL-4通过Bcl-2依赖性途径阻止B-CLL细胞凋亡。鉴于我们最近观察到来自B-CLL患者的新鲜T细胞表达IL-4 mRNA，我们提出IL-4通过阻止恶性B细胞的死亡和增殖在CLL疾病的发病机制中起重要作用。
B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells arrested at the intermediate stage of their differentiation. We previously showed that interleukin 4 (IL-4) not only inhibits but also prevents the proliferation of B-CLL cells. We report here that IL-4 protects the B-CLL cells from death by apoptosis (programmed cell death [PCD]). IL-4 inhibits spontaneous and hydrocortisone (HC)-induced PCD of highly purified B cells from 12 unselected CLL patients, as shown by sustained cell viability and lack of DNA fragmentation. IL-1, -2, -3, - 5, -6, -7, tumor necrosis factor alpha, and transforming growth factor beta have no protective effect. The in vitro rescue from apoptosis by IL-4 is reflected by an increased expression of Bcl-2 protein, a proto- oncogene directly involved in the prolongation of cell survival in vivo and in vitro. Hence, IL-4-treated B-CLL cells express significantly more Bcl-2 than unstimulated, HC-treated, or fresh B-CLL cells. Furthermore, subcutaneous injection of IL-4 into one CLL patient enhances Bcl-2 protein expression in the leukemic B cells. These data may suggest that IL-4 prevents apoptosis of B-CLL cells using a Bcl-2- dependent pathway. Given our recent observations that fresh T cells from B-CLL patients express IL-4 mRNA, we propose that IL-4 has an essential role in the pathogenesis of CLL disease, by preventing both the death and the proliferation of the malignant B cells.
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影响因子：
64.8
作者：
SMITH, CA;WILLIAMS, GT;OWEN, JJT
通讯作者：
OWEN, JJT
影响因子：
15.9
作者：
FOURNIER, S;DELESPESSE, G;SARFATI, M
通讯作者：
SARFATI, M
DOI：
10.1073/pnas.88.16.6961
发表时间：
1991-08-01
影响因子：
11.1
作者：
HOCKENBERY, DM;ZUTTER, M;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
影响因子：
5.4
作者：
LIU, YJ;MASON, DY;MACLENNAN, ICM
通讯作者：
MACLENNAN, ICM
白介素4抵消了白介素2诱导的单克隆B细胞增殖。
影响因子：
15.3
作者：
Karray, S;DeFrance, T;Merle-Beral, H;Banchereau, J;Debre, P;Galanaud, P
通讯作者：
Galanaud, P