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白细胞介素-15/白细胞介素-15受体系统在肿瘤来源的人B细胞系中的旁分泌功能。

Juxtacrine function of interleukin-15/interleukin-15 receptor system in tumour derived human B-cell lines.

作者信息

Tsukamoto K, Huang Y C, Dorsey W C, Carns B, Sharma V

机构信息

Laboratory of Cytokine Research, Department of Biology, University of West Florida, Pensacola, Florida 10032, USA.

出版信息

Clin Exp Immunol. 2006 Dec;146(3):559-66. doi: 10.1111/j.1365-2249.2006.03240.x.

Abstract

Interleukin-15 (IL-15) is a cytokine that induces proliferation and promotes cell survival of human T, B and NK cells. IL-15 and interleukin-2 (IL-2) exhibit a similar spectrum of immune effects and share the IL-2 receptor (IL-2R) subunits IL-2Rbeta and IL-2Rgamma(c) for signalling in haematopoietic cells. Furthermore, each cytokine has a private alpha receptor, namely IL-2Ralpha for IL-2 and IL-15Ralpha for IL-15, that functions in ligand binding. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) methods, the expression and secretion of IL-15 and IL-15Ralpha in tumour-derived B-cell lines were studied. The results as presented in this study identify that IL-15 mRNA is predominantly expressed in EBV positive (EBV(+)) B-cell lines, although IL-15Ralpha is ubiquitously and constitutively expressed in all these B-cell lines. Although no detectable levels of IL-15 protein secretion were observed in any of these cell lines, we were able to detect membrane-bound expression of IL-15 protein by FACS analysis in some cell lines. These data imply that the IL-15/IL-15R system requires complex regulatory mechanisms for protein secretion. Taken together, we speculate that these results suggest a juxtacrine, intracrine function for IL-15/IL-15R.

摘要

白细胞介素-15(IL-15)是一种可诱导人T细胞、B细胞和NK细胞增殖并促进其存活的细胞因子。IL-15和白细胞介素-2(IL-2)具有相似的免疫效应谱,并共享IL-2受体(IL-2R)亚基IL-2Rβ和IL-2Rγ(c),以便在造血细胞中进行信号传导。此外,每种细胞因子都有一个特有的α受体,即IL-2的IL-2Rα和IL-15的IL-15Rα,其作用是结合配体。采用逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)方法,研究了肿瘤来源的B细胞系中IL-15和IL-15Rα的表达及分泌情况。本研究呈现的结果表明,IL-15 mRNA主要在EB病毒阳性(EBV(+))的B细胞系中表达,尽管IL-15Rα在所有这些B细胞系中均普遍且组成性表达。虽然在任何这些细胞系中均未观察到可检测水平的IL-15蛋白分泌,但通过流式细胞术分析,我们在一些细胞系中检测到了IL-15蛋白的膜结合表达。这些数据表明,IL-�15/IL-15R系统的蛋白分泌需要复杂的调节机制。综上所述,我们推测这些结果提示IL-15/IL-15R具有旁分泌、自分泌功能。

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