Scheel-Toellner D, Pilling D, Akbar A N, Hardie D, Lombardi G, Salmon M, Lord J M
MRC Centre for Immune Regulation, Division of Immunity and Infection, University of Birmingham, Birmingham, GB.
Eur J Immunol. 1999 Aug;29(8):2603-12. doi: 10.1002/(SICI)1521-4141(199908)29:08<2603::AID-IMMU2603>3.0.CO;2-L.
Type I interferons rescue activated human T cells from cytokine deprivation-induced apoptosis. Our data now show that IFN-beta also rapidly inhibits apoptotic signals induced through the Fas receptor (CD95) in human T cells. To identify upstream signaling elements that could be targets of IFN-beta, we have studied protein kinase C (PKC). PKC-delta is actively involved in the regulation of apoptosis and immunofluorescence staining revealed that early in apoptosis PKC-delta accumulated in the nucleus. Addition of IFN-beta to T cells already deprived of survival factors or treated with anti-Fas antibody caused a rapid retranslocation of PKC-delta away from the nucleus. Furthermore, the generation of a constitutively active catalytic fragment by cleavage of PKC-delta by caspase 3 occurred only after translocation of full-length PKC-delta to the nucleus. IFN-beta also inhibited caspase 3 and the proteolytic activation of PKC-delta. We conclude from these studies that nuclear translocation of PKC-delta is an early event in T cell apoptosis and that IFN-beta rapidly reverses this process.
I型干扰素可拯救活化的人类T细胞，使其免受细胞因子剥夺诱导的凋亡。我们现在的数据表明，IFN-β还能迅速抑制人类T细胞中通过Fas受体（CD95）诱导的凋亡信号。为了确定可能作为IFN-β作用靶点的上游信号元件，我们研究了蛋白激酶C（PKC）。PKC-δ积极参与凋亡调控，免疫荧光染色显示，在凋亡早期PKC-δ在细胞核中积累。向已经缺乏生存因子或用抗Fas抗体处理的T细胞中添加IFN-β，会导致PKC-δ迅速从细胞核重新定位到细胞核外。此外，只有在全长PKC-δ转移到细胞核后，caspase 3切割PKC-δ产生组成型活性催化片段的过程才会发生。IFN-β还抑制caspase 3以及PKC-δ的蛋白水解激活。我们从这些研究中得出结论，PKC-δ的核转位是T细胞凋亡中的早期事件，而IFN-β能迅速逆转这一过程。
