Department of Hematology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Oncol Rep. 2018 Jun;39(6):3064-3072. doi: 10.3892/or.2018.6367. Epub 2018 Apr 12.
Interleukin‑9 (IL‑9) can function as both a positive and negative regulator of immune response, however the role of IL‑9 in tumor immunity is poorly understood. Chronic lymphocytic leukemia (CLL) is the most common chronic lympho‑proliferative disorder. Twenty CLL patients from 2010 to 2011 were recruited in the study. Expression and phosphorylation of transcription factor STAT3 and differential microRNAs (miRs) in peripheral blood mononuclear cells (PBMCs) from CLL patient samples were analyzed. In a previous study, we found a high level of IL‑9 in CLL patients. Concomitantly, overexpression of pSTAT3, miR‑155, and miR‑21 were observed in PBMCs from CLL patients in the present study. To elucidate whether there was interaction among IL‑9, STAT3, miR‑155, and miR‑21, MEC‑1 cells were used for further study. Our results revealed that there was no detectable IL‑9 in the culture medium of MEC‑1 cells. However, the IL‑9 protein could be detected using western blotting in MEC‑1 cells. Notably, when recombinant human IL‑9 (rIL‑9) was added to the medium of culturing MEC‑1 cells, the expression levels of pSTAT3 and IL‑9 in MEC‑1 cells were increased in a time‑dependent manner, which could be blocked by STAT3 inhibitor. Both miR‑155 and miR‑21 could increase IL‑9 expression, which could also be suppressed by the inhibitor of STAT3. Our data indicated that the existence of the novel 'extracellular IL‑9/pSTAT3/miR‑155/miR‑21/intracellular IL‑9' positive feedback system in CLL cells, provides a novel insight in the pathogenesis and possible therapeutic strategy of CLL.
白细胞介素-9 (IL-9) 可作为免疫反应的正调节剂和负调节剂发挥作用，但 IL-9 在肿瘤免疫中的作用尚不清楚。慢性淋巴细胞白血病 (CLL) 是最常见的慢性淋巴增生性疾病。本研究纳入了 2010 年至 2011 年间的 20 名 CLL 患者。分析了 CLL 患者外周血单个核细胞 (PBMC) 中转录因子 STAT3 的表达和磷酸化以及差异 microRNAs (miRs)。在之前的研究中，我们发现 CLL 患者的 IL-9 水平较高。同时，在本研究中，我们观察到 CLL 患者 PBMC 中 pSTAT3、miR-155 和 miR-21 的过度表达。为了阐明 IL-9、STAT3、miR-155 和 miR-21 之间是否存在相互作用，我们使用 MEC-1 细胞进行了进一步研究。我们的结果表明，在 MEC-1 细胞的培养基中未检测到可检测的 IL-9。然而，在 MEC-1 细胞中可通过 Western blot 检测到 IL-9 蛋白。值得注意的是，当将重组人 IL-9 (rIL-9) 添加到 MEC-1 细胞的培养基中时，MEC-1 细胞中 pSTAT3 和 IL-9 的表达水平呈时间依赖性增加，可被 STAT3 抑制剂阻断。miR-155 和 miR-21 均可增加 IL-9 的表达，该作用也可被 STAT3 抑制剂抑制。我们的数据表明，在 CLL 细胞中存在新型“细胞外 IL-9/pSTAT3/miR-155/miR-21/细胞内 IL-9”正反馈系统，为 CLL 的发病机制和可能的治疗策略提供了新的见解。
