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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function
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Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function

机译：骨髓增生异常综合症和慢性粒单核细胞白血病中IL-32的失调调节细胞凋亡并损害NK功能

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摘要

TNFα levels are elevated in the marrows of patients with myelodysplastic syndrome (MDS) and are associated with high rates of apoptosis, which contributes to hematopoietic failure. We observed that exposure of human marrow stroma cell lines HS5 and HS27a to TNFα increases levels of IL-32 mRNA. IL-32, in turn, induces TNFα. Marrow stroma from patients with MDS expressed 14- to 17-fold higher levels of IL-32 mRNA than healthy controls. In contrast, cells from patients with chronic myelomonocytic leukemia (CMML) expressed only one tenth the level of IL-32 measured in healthy controls. Human KG1a leukemia cells underwent apoptosis when cocultured with HS5 stromal cells, but knockdown of IL-32 in the stromal cells by using siRNA abrogated apoptosis in the leukemia cells. IL-32 knockdown cells also showed dysregulation of VEGF and other cytokines. Furthermore, CD56~+ natural killer cells from patients with MDS and CMML expressed IL-32 at lower levels than controls and exhibited reduced cytotoxic activity, which was unaffected by IL-2 treatment. We propose that IL-32 is a marrow stromal marker that distinguishes patients with MDS and CMML. Furthermore, IL-32 appears to contribute to the pathophysiology of MDS and may be a therapeutic target.
机译：骨髓增生异常综合症（MDS）患者的骨髓中TNFα水平升高，并与高凋亡率相关，这有助于造血功能衰竭。我们观察到人类骨髓基质细胞系HS5和HS27a暴露于TNFα会增加IL-32 mRNA的水平。 IL-32依次诱导TNFα。来自MDS患者的骨髓基质表达的IL-32 mRNA水平比健康对照组高14至17倍。相反，来自慢性粒细胞性单核细胞白血病（CMML）患者的细胞表达的IL-32水平仅为健康对照中的十分之一。人KG1a白血病细胞与HS5基质细胞共培养时发生凋亡，但是通过使用siRNA敲低基质细胞中IL-32可以消除白血病细胞的凋亡。 IL-32敲低细胞还显示出VEGF和其他细胞因子的失调。此外，来自MDS和CMML患者的CD56 +自然杀伤细胞表达IL-32的水平低于对照组，并显示出降低的细胞毒活性，不受IL-2治疗的影响。我们建议IL-32是一种区分MDS和CMML患者的骨髓基质标记。此外，IL-32似乎有助于MDS的病理生理，并且可能是治疗靶点。

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