Tong Xiaoling, Zhang Lijun, Zhang Li, Hu Meng, Leng Jun, Yu Beibei, Zhou Beibei, Hu Yi, Zhang Qiuping
Department of Immunology, College of Basic Medical Sciences, Wuhan University, Donghu Road 185, Wuchang, Wuhan 430071, China.
Cell Mol Immunol. 2009 Jun;6(3):181-9. doi: 10.1038/cmi.2009.25.
In previous study, we found that the chemokine receptor 9 (CCR9) was highly expressed on CD4+ T cells from patients with T-cell lineage acute lymphocytic leukemia (T-ALL) and mediated leukemia cell infiltration and metastasis. Combined use of interleukin 2 (IL-2) and IL-4 promoted the internalization of CCR9 and therefore attenuated leukemia cell infiltration and metastasis. In this study, we preliminarily investigated the mechanism of internalization of CCR9 on MOLT4 cell model (a human leukemia T-cell line, naturally expresses CCR9) and found that IL-2 upregulated the cell surface expression of IL-4Ralpha (CD124) greatly, whereas IL-4 had no significant influence on alpha (CD25) and beta subunits (CD122) of IL-2R. Moreover, specific inhibitors, such as staurosporine, H89 and heparin, inhibited internalization of CCR9, which indicated a role of protein kinase C (PKC) and G protein-coupled kinase 2 (GRK2), respectively. Furthermore, GRK2 was upregulated and translocated to cell membrane in IL-2 and IL-4 treated cells which indicated that PKC could be a prerequisite for GRK2 activity.
在先前的研究中，我们发现趋化因子受体9（CCR9）在T细胞系急性淋巴细胞白血病（T-ALL）患者的CD4+ T细胞上高表达，并介导白血病细胞的浸润和转移。白细胞介素2（IL-2）和IL-4联合使用可促进CCR9的内化，从而减弱白血病细胞的浸润和转移。在本研究中，我们在MOLT4细胞模型（一种天然表达CCR9的人白血病T细胞系）上初步研究了CCR9内化的机制，发现IL-2显著上调了IL-4Rα（CD124）的细胞表面表达，而IL-4对IL-2R的α亚基（CD25）和β亚基（CD122）没有显著影响。此外，特异性抑制剂，如星形孢菌素、H89和肝素，可抑制CCR9的内化，这分别表明蛋白激酶C（PKC）和G蛋白偶联激酶2（GRK2）发挥了作用。此外，在经IL-2和IL-4处理的细胞中，GRK2上调并转位至细胞膜，这表明PKC可能是GRK2活性的先决条件。
