The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression.
The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression.
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DOI：
10.4049/jimmunol.160.1.134
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发表时间：
1998-01
影响因子：
4.4
通讯作者：
M. Faris;Niels Kokot;K. Latinis;S. Kasibhatla;Douglas R. Green;G. Koretzky;Andre E. Nel
中科院分区：
文献类型：
--
作者：
M. Faris;Niels Kokot;K. Latinis;S. Kasibhatla;Douglas R. Green;G. Koretzky;Andre E. Nel
T淋巴细胞在受到包括紫外线照射和伽马射线辐射等细胞应激时会发生凋亡。然而，应激刺激诱导凋亡的机制尚未完全清楚。虽然应激刺激会诱导c - Jun N末端激酶（JNK）通路的激活，但不清楚JNK级联是细胞死亡的结果而被激活，还是该级联参与诱导凋亡。我们利用在四环素调控表达系统中转染了显性激活（DA）-丝裂原活化蛋白激酶激酶激酶（MEKK1）的Jurkat T细胞系，发现DA - MEKK1的表达导致Jurkat细胞凋亡，同时伴有JNK的持续激活。此外，DA - MEKK1诱导Fas配体（FasL）在细胞表面表达和mRNA表达，以及FasL启动子的激活。干扰Fas/FasL相互作用可阻止DA - MEKK1介导的凋亡。在比较不同应激刺激与DA - MEKK1的作用时，我们发现紫外线、伽马射线辐射和茴香霉素在诱导FasL表达和细胞死亡的同时，会使JNK持续激活。此外，这些刺激也会增强FasL在细胞表面的表达。干扰Fas/FasL相互作用可抑制茴香霉素诱导的凋亡，但不能抑制紫外线或伽马射线辐射诱导的凋亡。我们的数据表明，虽然JNK通路通过调节FasL表达促进T淋巴细胞中应激诱导的凋亡，但并非所有应激刺激都使用相同的细胞死亡途径。
T lymphocytes undergo apoptosis in response to cellular stress, including UV exposure and gamma irradiation. However, the mechanism by which stress stimuli induce apoptosis is not well understood. While stress stimuli induce the activation of the c-Jun N-terminal kinase (JNK) pathway, it is not clear whether the JNK cascade is activated as a result of cell death or whether the cascade participates in inducing apoptosis. Using a Jurkat T cell line transfected with dominant active (DA)-mitogen-activated protein kinase kinase kinase (MEKK1) in a tetracycline-regulated expression system, we found that expression of DA-MEKK1 results in the apoptosis of Jurkat cells in parallel with prolonged JNK activation. Moreover, DA-MEKK1 induced Fas ligand (FasL) cell surface and mRNA expression, as well as FasL promoter activation. Interference with Fas/FasL interaction prevented DA-MEKK1-mediated apoptosis. In comparing the effect of different stress stimuli to DA-MEKK1, we found that UV, gamma irradiation, and anisomycin prolonged JNK activation in parallel with FasL expression and onset of cell death. In addition, these stimuli also enhance cell surface expression of FasL. Interference with Fas/FasL interactions inhibited anisomycin but not UV- or gamma irradiation-induced apoptosis. Our data show that while the JNK pathway contributes to stress-induced apoptosis in T lymphocytes by regulating FasL expression, not all stress stimuli use the same cell death pathway.