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首页> 外文期刊>Journal of Cellular Physiology >Role of the RANKL/RANK system in the induction of interleukin-8 (IL-8) in B chronic lymphocytic leukemia (B-CLL) cells.
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Role of the RANKL/RANK system in the induction of interleukin-8 (IL-8) in B chronic lymphocytic leukemia (B-CLL) cells.

机译:RANKL /角色等级系统的感应interleukin-8(引发)B慢性淋巴细胞细胞白血病(B-CLL)。

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摘要

B chronic lymphocytic leukemia (B-CLL) cells express several members of the tumor necrosis factor (TNF) family, such as CD40L, CD30L, and TRAIL. By using the cDNA microarray technology, B-CLL samples were found to overexpress receptor activator of nuclear factor kB (NF-kB) ligand (RANKL), as compared to normal CD19(+) B cells. These findings were validated at the protein level by Western blot and flow cytometry analyses. Moreover, unlike primary normal B cells, leukemic B-CLL cells showed surface expression of RANK, the cognate transmembrane receptor of RANKL. When added in vitro to B-CLL cultures, either alone or in association with chlorambucil or fludarabine, recombinant RANKL did not significantly modulate cell viability, and it minimally affected the IL-8 expression/release. On the other hand, treatment with RANK-Fc chimera potently upregulated the release of IL-8 in the B-CLL culture supernatants, suggesting involvement of reverse signaling through transmembrane RANKL in IL-8 induction. In turn, exposure of B-CLL cells to recombinant IL-8 significantly decreased spontaneous apoptosis as well as chlorambucil- and fludarabine-mediated cytoxicity in B-CLL cells. Since IL-8 has been implicated in progression of B-CLL disease, our findings suggest that, by upregulating IL-8, the RANKL/RANK system may contribute to the pathogenesis of B-CLL.
机译:B慢性淋巴细胞白血病(B-CLL)细胞表达肿瘤坏死的几位因子(TNF)的家庭,如CD40L、CD30L,线索。B-CLL样本被发现过表达受体活化剂的核因子kB (NF-kB)配体(RANKL),相比正常CD19 + B细胞。这些研究结果验证了在蛋白质通过免疫印迹和流式细胞术水平分析。细胞白血病B-CLL细胞显示表面的表达,同源跨膜RANKL的受体。文化中,无论是单独或与苯丁酸氮芥或氟达拉滨,RANKL重组没有显著的调节细胞生存能力,它引发的影响最小表达式或发布。与RANK-Fc嵌合体强有力地调节释放引发B-CLL文化浮在表面的,表明反向的参与通过跨膜信号RANKL在引发归纳。重组引发大幅下降自发凋亡以及苯丁酸氮芥-并在B-CLL fludarabine-mediated细胞毒细胞。B-CLL疾病的进展,我们的发现表明,移植引发的RANKL /等级系统可能导致B-CLL的发病机理。

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