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由STAT6激活诱导的IL-9过表达促进慢性淋巴细胞白血病的发病机制。

Overexpression of IL-9 induced by STAT6 activation promotes the pathogenesis of chronic lymphocytic leukemia.

作者信息

Chen Na, Lu Kang, Li Peipei, Lv Xiao, Wang Xin

机构信息

Department of Hematology, Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.

Department of Hematology, Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China ; Institute of Diagnostics, School of Medicine, Shandong University Jinan, Shandong, China.

出版信息

Int J Clin Exp Pathol. 2014 Apr 15;7(5):2319-23. eCollection 2014.

Abstract

Chronic lymphocytic leukemia (CLL) is a common leukemia in adults, but its pathogenesis is still poorly understood. Recently, extensive evidence suggests that the malignant cells of CLL patients secrete a range of cytoprotective cytokines including interleukin-4 (IL-4). IL-4 induced the rapid phosphorylation(p) and activation of the signal transducer and activator of transcription (STAT)-6 transcription factor in CLL cells in vitro. Interleukin-9 (IL-9) is not expressed by Th2 and Th9 cells in the absence of STAT6 expression. To elucidate whether there was a function link between IL-9 and STAT6 in CLL, MEC-1 cells were analyzed using RT-PCR, and western blot. Interestingly, when added with recombinant human IL-4 (rIL-4) in culturing MEC-1 cells, expressions of p-STAT6 and IL-9 in MEC-1 cells increased at a time-dependent manner and their expressions could be inhibited by STAT6 inhibitor. Our data indicated that the upregulation of IL-9 induced by pSTAT6 may be involved in the pathogenesis of CLL.

摘要

慢性淋巴细胞白血病(CLL)是成人常见的白血病,但其发病机制仍知之甚少。最近,大量证据表明,CLL患者的恶性细胞分泌一系列细胞保护细胞因子,包括白细胞介素-4(IL-4)。在体外,IL-4可诱导CLL细胞中信号转导子和转录激活子(STAT)-6转录因子快速磷酸化(p)并激活。在没有STAT6表达的情况下,Th2和Th9细胞不表达白细胞介素-9(IL-9)。为了阐明CLL中IL-9与STAT6之间是否存在功能联系,使用逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法对MEC-1细胞进行了分析。有趣的是,在培养MEC-1细胞时加入重组人IL-4(rIL-4)后,MEC-1细胞中p-STAT6和IL-9的表达呈时间依赖性增加,且其表达可被STAT6抑制剂抑制。我们的数据表明,pSTAT6诱导的IL-9上调可能参与了CLL的发病机制。

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