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Evaluating the mechanism underlying antitumor effect of interleukin 27 on B cells of chronic lymphocytic leukemia patients.
Journal of Cellular Physiology ( IF 5.6 ) Pub Date : 2020-05-07 , DOI: 10.1002/jcp.29747
Ehsan Manouchehri-Doulabi 1, 2, 3 , Somaye Abbaspour 1, 2 , Shahrbano Rostami 4 , Mohammad Faranoush 5 , Farahnaz Ghahramanfard 1, 2 , Fatemeh Pak 1 , Mehdi Barati 6, 7 , Parviz Kokhaei 1, 2, 8 , Amir A Momtazi-Borojeni 9, 10
Affiliation  

Chronic lymphocyte leukemia (CLL) is a B‐cell malignancy resisted to apoptosis. Recently, some studies indicated that cytokines such as interleukin 27 (IL‐27) can reduce B‐cell proliferation. The aim of this study is to evaluate the mechanism underlying the proapoptotic effect of IL‐27 on B cells of patients with CLL in comparison with B cells of normal subjects. The effect of IL‐27 on the antitumor activity of natural killer (NK) and T cells was also evaluated. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CLL and 15 normal subjects. B cells and PBMCs were cocultured with IL‐27 and B cells apoptosis to evaluate proliferation. Both messenger RNA and protein expression of IL‐27 and IL‐27 receptor were determined using flow cytometry and real‐time polymerase chain reaction analysis. To evaluate the apoptotic effect of IL‐27 on B cells of patients with CLL, Annexin V‐FITC and 7‐AAD (BioLegend) fluorescent dyes were used. In addition, the IL‐27 effect on activation of T cell and NK cell was determined by determining CD96 molecule expression. IL‐27 and IL‐27 receptor expression in patients with CLL was significantly lower than that of normal subjects (p < .05). IL‐27 enhanced apoptosis of B cells in patients with CLL (p < .05) but this effect was not significantly observed in B cells of normal subjects (p > .05). Consequently, IL‐27 reduced the proliferation of B cells and enhanced NK cell activity (p < .05). IL‐27, through inducing apoptosis, can exert an inhibitory effect on cancer B cells of CLL patients with minimal effect on normal B cells.

中文翻译:

评价白介素27对慢性淋巴细胞白血病患者B细胞抗肿瘤作用的潜在机制。

慢性淋巴细胞白血病(CLL)是抵抗细胞凋亡的B细胞恶性肿瘤。最近,一些研究表明,诸如白介素27(IL-27)之类的细胞因子可以减少B细胞增殖。这项研究的目的是评估与正常受试者的B细胞相比,IL-27对CLL患者B细胞促凋亡作用的潜在机制。还评估了IL‐27对自然杀伤(NK)和T细胞的抗肿瘤活性的影响。从35名CLL患者和15名正常受试者中分离出外周血单个核细胞(PBMC)。将B细胞和PBMC与IL-27和B细胞凋亡共培养以评估增殖。使用流式细胞仪和实时聚合酶链反应分析确定信使RNA和IL‐27和IL‐27受体的蛋白表达。为了评估IL‐27对CLL患者B细胞的凋亡作用,使用了Annexin V‐FITC和7‐AAD(BioLegend)荧光染料。此外,通过测定CD96分子的表达来确定IL‐27对T细胞和NK细胞活化的影响。CLL患者的IL‐27和IL‐27受体表达明显低于正常受试者(p  <.05)。IL-27增强了CLL患者B细胞的凋亡(p  <.05),但在正常受试者的B细胞中未观察到这种作用(p  > .05)。因此,IL- 27减少了B细胞的增殖并增强了NK细胞的活性(p  <.05)。IL-27通过诱导细胞凋亡,可以对CLL患者的B细胞产生抑制作用,而对正常B细胞​​的作用却很小。
更新日期:2020-05-07
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