Jang Ji-Young, Lee Choong-Eun
Department of Biological Science and Institute for Basic Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Cell Immunol. 2003 Nov;226(1):11-9. doi: 10.1016/j.cellimm.2003.11.004.
IL-4 and IFN-gamma are prototypical Th2 and Th1 cytokines, respectively. They reciprocally regulate a number of genes involved in Th1 vs Th2 immune balance. Using DD-PCR analysis, adenine nucleotide translocase (ANT) 3, an enzyme which exchanges ATP and ADP through mitochondrial membrane, has been identified as a novel target counter-regulated by IL-4 and IFN-gamma. We have observed that IL-4 and IFN-gamma each up-regulates ANT3 in T cells both at mRNA and protein levels, while cotreatment of IL-4 and IFN-gamma counter-regulates ANT3 expression. In contrast, other isoforms of ANT were not affected by IL-4 or IFN-gamma. Emplyoing transfection and overexpression of STAT6 and STAT1 in STAT-deficient cells, we demonstrate that induction of ANT3 by IL-4 and IFN-gamma proceeds via pathways involving STAT6 and STAT1, respectively. Furthermore, regulation of ANT3 expression by IL-4 and IFN-gamma correlated with the modulation T cell survival by these cytokines from dex-induced apoptosis. Considering the critical role of mitochondrial ANTs in energy metabolism and apoptosis, ANT3 regulation by IL-4 and IFN-gamma may have a functional implication in cytokine-mediated T cell survival.
IL-4和IFN-γ分别是典型的Th2和Th1细胞因子。它们相互调节许多参与Th1与Th2免疫平衡的基因。利用差异显示PCR（DD-PCR）分析，已鉴定出腺嘌呤核苷酸转位酶（ANT）3是一种通过线粒体膜交换ATP和ADP的酶，它是受IL-4和IFN-γ反向调节的新靶点。我们观察到，IL-4和IFN-γ在mRNA和蛋白质水平上均上调T细胞中的ANT3，而IL-4和IFN-γ共同处理则反向调节ANT3的表达。相比之下，ANT的其他同工型不受IL-4或IFN-γ的影响。通过在STAT缺陷细胞中转染并过表达STAT6和STAT1，我们证明IL-4和IFN-γ对ANT3的诱导分别通过涉及STAT6和STAT1的途径进行。此外，IL-4和IFN-γ对ANT3表达的调节与这些细胞因子对T细胞存活的调节相关，可使其免受地塞米松诱导的凋亡。考虑到线粒体ANTs在能量代谢和凋亡中的关键作用，IL-4和IFN-γ对ANT3的调节可能在细胞因子介导的T细胞存活中具有功能意义。
