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首页> 外文期刊>Cytokine >Expression patterns of leptin receptor (OB-R) isoforms and direct in vitro effects of recombinant leptin on OB-R, leptin expression and cytokine secretion by human hematopoietic malignant cells.
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Expression patterns of leptin receptor (OB-R) isoforms and direct in vitro effects of recombinant leptin on OB-R, leptin expression and cytokine secretion by human hematopoietic malignant cells.

机译：瘦素受体（OB-R）亚型的表达模式以及重组瘦素对人造血恶性肿瘤细胞OB-R，瘦素表达和细胞因子分泌的直接体外作用。

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摘要

Several studies have implicated leptin in the pathophysiology of neoplasias. We investigated the direct effect of leptin on malignant hematopoietic tissue that included: primary acute myeloid leukemia (AML) cells, leukemic cell lines and bone marrow biopsies from multiple myeloma (MM) patients. PBMC, T-cells, B-cells and monocytes from healthy subjects served as controls. We defined the patterns of OB-R isoform expression in AML cells and leukemic cell lines in comparison to control cells by RT-PCR. rLeptin upregulated the expression of OB-R and endogenous leptin in AML blasts and certain cell lines but not in control cells. Cytometric Bead Array analysis of pro- and anti-inflammatory cytokines showed that rleptin upregulates IL-6 secretion by AML cells, various cytokines by the leukemic cell lines tested and IL-10 secretion by control PBMC, contributed by monocytes. Western immunoblotting revealed that the effect of rleptin was independent of JAK-2/phospho-JAK-2 protein levels. Finally, MM biopsies stained positive for leptin and, to a lesser extend, OB-R. Immunoreactivity was confined mostly to the nucleus of the myeloma cells. Normal myelocytes, promyelocytes and megakaryocytes stained weakly positive, and erythroid cells were constantly negative. We propose that the leptin/OB-R system is strongly and directly involved in supporting the growth of hematopoietic malignancies.
机译：几项研究表明瘦素与肿瘤形成的病理生理有关。我们调查了瘦素对恶性造血组织的直接作用，其中包括：多发性骨髓瘤（MM）患者的原发性急性髓细胞性白血病（AML）细胞，白血病细胞系和骨髓活检。来自健康受试者的PBMC，T细胞，B细胞和单核细胞用作对照。通过RT-PCR，我们定义了AML细胞和白血病细胞系中OB-R亚型表达的模式，与对照细胞相比。 rLeptin在AML母细胞和某些细胞系中上调OB-R和内源性瘦素的表达，但在对照细胞中则不上调。对促炎和抗炎细胞因子的细胞计数珠阵列分析表明，rleptin上调AML细胞的IL-6分泌，测试的白血病细胞系上调各种细胞因子，而对照PBMC分泌IL-10，由单核细胞贡献。 Western免疫印迹表明，rleptin的作用与JAK-2 / phospho-JAK-2蛋白水平无关。最后，MM活检对瘦素和OB-R呈阳性染色。免疫反应性主要局限于骨髓瘤细胞的细胞核。正常的骨髓细胞，早幼粒细胞和巨核细胞染色呈弱阳性，而红系细胞则持续呈阴性。我们建议，瘦素/ OB-R系统强烈且直接参与支持造血系统恶性肿瘤的生长。

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