Amos C L, Woetmann A, Nielsen M, Geisler C, Odum N, Brown B L, Dobson P R
Department of Human Metabolism and Clinical Biochemistry, Cellular Signalling, Institute of Endocrinology, University of Sheffield Medical School, Sheffield, S10 2RX, U.K.
Cytokine. 1998 Sep;10(9):662-8. doi: 10.1006/cyto.1998.0351.
The effects of interleukin 7 (IL-7) on apoptosis in interleukin 2 (IL-2)-dependent, activated, primary, human T lymphocytes (hT cells) was examined. IL-7 (like IL-2) rescued cells from apoptosis, as measured by their cellular DNA profile and fragmentation. IL-2 also acted as a mitogen in these T cells. Both cytokines abrogated the dexamethasone-induced stimulation of Caspase 3 and prevented the cleavage of poly (ADP-ribose) polymerase (PARP), a substrate for the Caspase 3. IL-7 upregulated the expression of Bc1xL and counteracted the downregulation of this anti-apoptotic protein by the synthetic glucocorticoid, dexamethasone. Bcl-2 protein expression was uupregulated by IL-7 with or without dexamethasone, but Bc1-2 was expressed at a much lower level than BclxL in these cells. Levels of Bax did not markedly change on either cytokine stimulation or dexamethasone treatment. An unidentified 23-kDa band, which was recognized by the anti-Bc1-2 antibody, was induced by dexamthasone and suppressed by IL-7 and IL-2. This protein was subject to independent regulation as compared to the p26 Bc1-2 protein, suggesting that it may be a novel factor, possibly involved in the regulation of apoptosis. A clear role for IL-7 as a survival factor for cytokine withdrawal and glucocorticoid induced apoptosis in activated primary hT cells is implicated. In addition, regulation of BclxL and downstream inhibition of Caspase 3 activity may mediate this rescue signal.
研究了白细胞介素7（IL-7）对白细胞介素2（IL-2）依赖的、活化的、原代人T淋巴细胞（hT细胞）凋亡的影响。通过细胞DNA图谱和片段化检测发现，IL-7（与IL-2一样）可使细胞免于凋亡。IL-2在这些T细胞中也起有丝分裂原的作用。两种细胞因子均消除了地塞米松诱导的半胱天冬酶3的激活，并阻止了聚（ADP-核糖）聚合酶（PARP，半胱天冬酶3的底物）的裂解。IL-7上调了BclxL的表达，并抵消了合成糖皮质激素地塞米松对这种抗凋亡蛋白的下调作用。无论有无地塞米松，IL-7均可上调Bcl-2蛋白的表达，但在这些细胞中Bcl-2的表达水平远低于BclxL。在细胞因子刺激或地塞米松处理后，Bax水平均未发生明显变化。一种未鉴定的23 kDa条带可被抗Bcl-2抗体识别，它由地塞米松诱导产生，并被IL-7和IL-2抑制。与p26 Bcl-2蛋白相比，这种蛋白受到独立调控，提示它可能是一种新因子，可能参与凋亡调控。这表明IL-7在活化的原代hT细胞中作为细胞因子撤除和糖皮质激素诱导凋亡的存活因子具有明确作用。此外，BclxL的调控及半胱天冬酶3活性的下游抑制可能介导了这种挽救信号。
