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白细胞介素10在人骨髓瘤细胞系中的表达与产生

Expression and production of interleukin 10 in human myeloma cell lines.

作者信息

Otsuki T, Yamada O, Yata K, Sakaguchi H, Kurebayashi J, Yawata Y, Ueki A

机构信息

Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama, Japan.

出版信息

Br J Haematol. 2000 Dec;111(3):835-42.

Abstract

Recent investigations of the cytokine network surrounding myeloma cells have disclosed the importance of gp130-related cytokines including interleukin (IL)-6 for myeloma cell survival and proliferation, identification of IL-10 as a growth factor for myeloma cells, the close relationship between IL-10 and the receptors for gp130-related cytokines, and the growth enhancement effect of IL-11 and IL-7 on myeloma cells. In this study, IL-10 production was observed in three out of seven human myeloma cell lines examined and five (including three producing lines) out of 10 lines exhibited mRNA expression of IL-10. The IL-10 mRNA expression was also enhanced in approximately one third of primary specimens, whereas the IL-10 receptor (R) expression was not changed compared with that of normal component marrow controls. However, reverse transcription-polymerase chain reaction (RT-PCR) assay of various cytokines and their receptors showed no particular association with IL-10-producing myeloma lines compared with non-producing lines. Supplementing exogenous IL-10 or neutralization of the IL-10 signal by anti-IL-10 monoclonal antibody (mAb) in a culture conditions did not significantly affect myeloma cell growth regardless of expression of IL-10 or its receptor (IL-10R). However, supplement of anti-IL-10 mAb caused upregulation of certain genes such as IL-11, leukaemia inhibitory factor receptor (LIFR) and syndecan-1 in IL-10R-expressing cell lines. These findings indicate that the cytokine network surrounding myeloma cells is complicated and variable. In addition, IL-10 may modify this network and the cellular biological properties of myeloma cells rather than cell proliferation.

摘要

最近围绕骨髓瘤细胞的细胞因子网络研究揭示了包括白细胞介素(IL)-6在内的gp130相关细胞因子对骨髓瘤细胞存活和增殖的重要性,确定IL-10为骨髓瘤细胞的生长因子,IL-10与gp130相关细胞因子受体之间的密切关系,以及IL-11和IL-7对骨髓瘤细胞的生长增强作用。在本研究中,在所检测的7个人骨髓瘤细胞系中有3个观察到IL-10产生,10个细胞系中有5个(包括3个产生系)表现出IL-10的mRNA表达。在大约三分之一的原发性标本中IL-10 mRNA表达也增强,而与正常组成骨髓对照相比,IL-10受体(R)表达没有变化。然而,与不产生IL-10的细胞系相比,各种细胞因子及其受体的逆转录-聚合酶链反应(RT-PCR)分析显示与产生IL-10的骨髓瘤细胞系没有特定关联。在培养条件下补充外源性IL-10或用抗IL-10单克隆抗体(mAb)中和IL-10信号,无论IL-10或其受体(IL-10R)的表达如何,均未显著影响骨髓瘤细胞生长。然而,抗IL-10 mAb的补充导致IL-10R表达细胞系中某些基因如IL-11、白血病抑制因子受体(LIFR)和多配体蛋白聚糖-1上调。这些发现表明围绕骨髓瘤细胞的细胞因子网络复杂且多变。此外,IL-10可能改变该网络以及骨髓瘤细胞的细胞生物学特性而非细胞增殖。

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