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IRF2-INPP4B axis inhibits apoptosis of acute myeloid leukaemia cells via regulating T helper 1/2 cell differentiation.
Cell Biochemistry and Function ( IF 2.8 ) Pub Date : 2020-03-01 , DOI: 10.1002/cbf.3511
Feng Zhang 1 , Kai Zhu 1 , Lin Liu 1 , Junfeng Zhu 1 , Jiajia Li 1 , Pingping Zhang 1 , Zhongli Hu 2 , Yuan Yuan 1
Affiliation  

The interferon‐regulatory factor 2 (IRF2)‐inositol polyphosphate‐4‐phosphatase type‐II (INPP4B) axis has been shown to suppress cell apoptosis by inducing autophagy in acute myeloid leukaemia (AML) cells. T helper type 1 cell (Th1)/Th2 imbalance is involved in development of autophagy and AML. The aim of this study was to investigate whether IRF2‐INPP4B axis regulates autophagy and apoptosis of AML cells via regulating Th1/Th2 cell differentiation. The frequencies of Th2 cells and Th1 cells in transfected CD4+ T cells were determined by flow cytometry. The levels of TNF‐α, IFN‐γ, IL‐4, and IL‐13 in peripheral blood and transfected CD4+ T cells from AML patients and healthy donors were examined by ELISA assay. The mRNA levels of IRF2 and INPP4B in peripheral blood mononuclear cells (PBMCs) from AML patients and healthy donors were detected by qRT‐PCR. Autophagy was evaluated by green fluorescent protein (GFP)‐LC3 immunofluorescence and western blot analysis of autophagy‐associated proteins. AML cell apoptosis was detected by flow cytometry. In this study, elevated frequencies of Th2 cells and reduced frequencies of Th1 cells, as well as higher expression of IRF2 and INPP4B, were observed in PBMCs from AML patients relative to healthy donors. Furthermore, IRF2 inhibited Th1 cell differentiation and promoted Th2 cell differentiation through INPP4B. Moreover, we confirmed that IRF2‐INPP4B–mediated regulation of Th1/Th2 differentiation promoted autophagy and inhibited apoptosis of AML cells. Collectively, IRF2‐INPP4B axis regulates autophagy and apoptosis of AML cells via regulating Th1/Th2 cell differentiation.

中文翻译:

IRF2-INPP4B轴通过调节T辅助细胞1/2的分化抑制急性髓性白血病细胞的凋亡。

干扰素调节因子2(IRF2)-肌醇多磷酸-4-磷酸酶II型(INPP4B)轴已显示可通过诱导急性髓样白血病(AML)细胞自噬来抑制细胞凋亡。1型T辅助细胞(Th1)/ Th2不平衡与自噬和AML的发展有关。这项研究的目的是研究IRF2-INPP4B轴是否通过调节Th1 / Th2细胞分化来调节AML细胞的自噬和凋亡。通过流式细胞术测定转染的CD4 + T细胞中Th2细胞和Th1细胞的频率。用ELISA法检测AML患者和健康供体的外周血和转染的CD4 + T细胞中TNF-α,IFN-γ,IL-4和IL-13的水平。通过qRT-PCR检测AML患者和健康供者的外周血单个核细胞(PBMC)中IRF2和INPP4B的mRNA水平。通过绿色荧光蛋白(GFP)-LC3免疫荧光和自噬相关蛋白的蛋白质印迹分析来评估自噬。通过流式细胞术检测AML细胞凋亡。在这项研究中,相对于健康供体,在AML患者的PBMC中观察到了Th2细胞的升高频率和Th1细胞的降低频率,以及IRF2和INPP4B的更高表达。此外,IRF2通过INPP4B抑制Th1细胞分化并促进Th2细胞分化。此外,我们证实IRF2-INPP4B介导的Th1 / Th2分化调控可促进自噬并抑制AML细胞凋亡。总的来说,
更新日期:2020-03-01
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