Interferon-α induces apoptosis in human KB cells through a stress-dependent mitogen activated protein kinase pathway that is antagonized by epidermal growth factor
Interferon-α induces apoptosis in human KB cells through a stress-dependent mitogen activated protein kinase pathway that is antagonized by epidermal growth factor
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DOI：
10.1038/sj.cdd.4400550
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发表时间：
1999-08-01
影响因子：
12.4
通讯作者：
Tagliaferri, P
中科院分区：
文献类型：
--
作者：
Caraglia, M;Abbruzzese, A;Tagliaferri, P
我们已经证明，生长抑制浓度的干扰素- α 2重组（IFN α）增强了人表皮样癌KB细胞中表皮生长因子受体（EGF- r）的表达和信号传导活性。在这里，我们报道了暴露于IFN α的KB细胞发生凋亡细胞死亡，这种作用被EGF拮抗。我们还发现IFN α增强了热休克蛋白（HSP） HSP-70的表达。HSP-90和HSP-27激活nh2末端Jun激酶-1 （JNK-1）和p38丝裂原激活蛋白激酶，这是应激依赖性细胞内转导途径的靶酶。此外，通过质粒转染KB细胞获得的野生型JNK-1过表达可诱导细胞凋亡，而将野生型JNK-1（JNK-1(wt)）转染的细胞暴露于IFN α中可增强细胞凋亡。所有这些作用都可以通过向暴露于IFN α的亲本和JNK-1（wt）转染的KB细胞中添加EGF来中和。综上所述，EGF对KB细胞凋亡具有保护作用，同时可以拮抗IFN α引发的应激反应，并靶向应激途径末端激酶。
We have demonstrated that interferon-alpha 2-recombinant (IFN alpha) at growth inhibitory concentrations enhances the expression and signalling activity of the epidermal growth factor receptor (EGF-R) in human epidermoid carcinoma KB cells, Here we report that KB cells exposed to IFN alpha underwent apoptotic cell death and this effect was antagonized by EGF, We have also found that IFN alpha enhanced the expression of heat shock proteins (HSP) HSP-70, HSP-90 and HSP-27 and activated the NH2-terminal Jun kinase-1 (JNK-1) and p38 mitogen activated protein kinase, the target enzymes of a stress-dependent intracellular transduction pathway. Moreover, the overexpression of the wild-type JNK-1, obtained through plasmid transfection of KB cells, induced apoptosis which was potentiated by the exposure of wild-type JNK-1 (JNK-1(wt))-transfected cells to IFN alpha. All these effects were neutralized by the addition of EGF to parental and JNK-1(wt)-transfected KB cells exposed to IFN alpha. In conclusion, EGF has a protective effect on KB cells from apoptosis while antagonizing a stress response elicited by IFN alpha and targeted on the stress pathway terminal kinases.