NF-κB/Rel participation in the lymphokine-dependent proliferation of T lymphoid cells
NF-κB/Rel participation in the lymphokine-dependent proliferation of T lymphoid cells
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DOI：
10.4049/jimmunol.166.4.2218
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
Boothby, M
中科院分区：
文献类型：
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作者：
Mora, AL;Youn, J;Boothby, M
淋巴样细胞对 IL-2 和 IL-4 的增殖反应取决于细胞的激活，但激活增强细胞响应细胞因子能力的机制尚不完全清楚。 NF-κB/Rel 家族代表了在这种激活过程中诱导的一种信号转导途径。我们在这项研究中表明，通过表达 I kappaB α（与 NF-kappaB 解离的抑制蛋白）突变体（对信号诱导的降解具有抵抗力）（I kappaB α(DeltaN)）来抑制 NF-kappaB，会干扰响应 IL-4 和 IL-2 的增殖能力的获得。来自 I kappaB α(DeltaN) 转基因小鼠的胸腺细胞和 T 细胞表达正常水平的 IL-2R 亚基。然而，转基因细胞在IL-2的Stat5A激活处理中表现出显着的缺陷，并且在IL-4诱导的Stat5中观察到类似的缺陷。相反，抑制 NF-kappaB 的 T 淋巴细胞表现出正常的胰岛素受体底物 2 磷酸化，并且在 IL-4 刺激后 Stat6 激活和胰岛素受体底物 1 磷酸化仅适度降低。这些结果表明 NF-kappaB/ReI/I kappaB α 系统可以通过影响 Stat 转录因子家族诱导下游信号传导来调节细胞因子受体获能。
Proliferative responses of lymphoid cells to IL-2 and IL-4 depend on activation of the cells, but the mechanism(s) by which activation enhances cellular competence to respond to cytokines is not fully understood, The NF-kappaB/Rel family represents one signal transduction pathway induced during such activation. We show in this study that inhibition of NF-kappaB through the expression of an I kappaB alpha (inhibitory protein that dissociates from NF-kappaB) mutant refractory to signal-induced degradation (I kappaB alpha(DeltaN)) interfered with the acquisition of competence to proliferate in response to IL-4 as well as IL-2. Thymocytes and T cells from I kappaB alpha(DeltaN) transgenic mice expressed normal levels of IL-2R subunits. However, transgenic cells exhibited a dramatic defect in Stat5A activation treatment with IL-2, and a similar defect was observed for IL-4-induced Stat5. In contrast, T lymphoid cells with inhibition of NF-kappaB showed normal insulin receptor substrate-2 phosphorylation and only a modest decrease in Stat6 activation and insulin receptor substrate-1 phosphorylation after IL-4 stimulation, These results indicate that the NF-kappaB/ReI/I kappaB alpha system can regulate cytokine receptor capacitation through effects on the induction of downstream signaling by the Stat transcription factor family.