The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24
The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24
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DOI：
10.4049/jimmunol.168.12.6041
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发表时间：
2002-06-15
影响因子：
4.4
通讯作者：
Grimm, EA
中科院分区：
文献类型：
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作者：
Caudell, EG;Mumm, JB;Grimm, EA
黑色素瘤分化相关基因7 （mda-7）主要是在其肿瘤抑制活性的背景下进行研究的。尽管基于其在IL-10位点的基因位置及其在白细胞中的mRNA表达，mda-7被指定为IL-24，但没有功能证据支持这种细胞因子名称。为了进一步表征人免疫系统中MDA-7/IL-24的表达模式，我们检测了人PBMC中MDA-7/IL-24的蛋白水平。Western blot检测PHA和lps刺激的整个PBMC裂解液中MDA-7/IL-24，免疫组化检测PHA激活的CD56和CD19亚群中MDA-7/IL-24。通过检测MDA-7/IL-24对PBMC细胞因子分泌谱的影响，评估ad - mda7转染HEK 293细胞分泌的MDA-7/IL-24的生物学功能。在48小时内，通过ELISA检测，MDA-7/IL-24诱导人PBMC分泌高水平的IL-6、tnf - α和ifn - γ，低水平的il -1 β、IL-12和GM-CSF。在PBMC中加入IL-10可以抑制MDA-7/ il -24介导的对这些th1型细胞因子的诱导，提示这两个相关蛋白家族成员可能具有拮抗功能。因此，由于人类血液白细胞可以刺激产生MDA-7/IL-24，并通过表达次级细胞因子对MDA-7/IL-24作出反应，因此MDA-7/IL-24具有表达谱和主要功能属性，证明其被称为IL。
The melanoma differentiation-associated gene 7 (mda-7) has been studied primarily in the context of its tumor suppressor activity. Although mda-7 has been designated as IL-24 based on its gene location in the IL-10 locus and its mRNA expression in leukocytes, no functional evidence supporting this cytokine designation exists. To further characterize MDA-7/IL-24 expression patterns in the human immune system, MDA-7/IL-24 protein levels were examined in human PBMC. MDA-7/IL-24 was detected in PHA- and LPS-stimulated whole PBMC lysate by Western blot and in PHA-activated CD56 and CD19 subsets by immunohistochemistry. The biological function of MDA-7/IL-24, secreted from Ad-MDA7-transfected HEK 293 cells, was assessed by examining the effect of MDA-7/IL-24 on the cytokine secretion profile of PBMC. Within 48 h MDA-7/IL-24 induced secretion of high levels of IL-6, TNF-alpha, and IFN-gamma and low levels of IL-1beta, IL-12, and GM-CSF from human PBMC as measured by ELISA. The MDA-7/IL-24-mediated induction of these Th1-type cytokines was inhibited by the addition of IL-10 to the PBMC cultures, suggesting that these two related protein family members may provide antagonistic functions. Therefore, because human blood leukocytes can be stimulated to produce MDA-7/IL-24, as well as respond to MDA-7/IL-24 by expressing secondary cytokines, MDA-7/IL-24 has the expression profile, and major functional attributes that-justify its designation as an IL.