Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties.
Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties.
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DOI：
10.1016/j.taap.2012.09.002
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发表时间：
2012-11-15
影响因子：
3.8
通讯作者：
Chow, S. C.
中科院分区：
文献类型：
--
作者：
Lawrence, C. P.;Chow, S. C.
半胱天冬酶抑制剂苄氧羰基（Cbz）-l-Val-Ala-Asp（OMe）-氟甲基酮（z-VAD-FMK）和苄氧羰基（Cbz）-Ile-Glu（OMe）-Thr-Asp（OMe）-FMK（z-IETD-FMK）在无毒剂量下被发现是免疫抑制性的，并且在体外抑制由促分裂剂和IL-2诱导的人T细胞增殖。这两种半胱天冬酶抑制剂均能阻断活化的原代T细胞中的NF-κB，但对T细胞活化过程中IL-2和IFN-γ的分泌几乎没有抑制作用。然而，活化T细胞中IL-2受体α链（CD 25）的表达被z-VAD-FMK和z-IETD-FMK抑制，而早期活化T细胞标志物CD 69的表达不受影响。在通过抗原受体的原代T细胞活化期间，胱天蛋白酶-8和胱天蛋白酶-3都被活化并加工成它们各自的亚基，但胱天蛋白酶抑制剂对这两种胱天蛋白酶的加工没有任何影响。与此形成鲜明对比的是，在活化的原代T细胞和Jurkat T细胞中，两种半胱天冬酶抑制剂在FasL诱导的凋亡期间容易地阻断凋亡和半胱天冬酶的活化。总的来说，结果表明z-VAD-FMK和z-IETD-FMK在体外都是免疫抑制性的，并且抑制T细胞增殖而不阻断半胱天冬酶-8和半胱天冬酶-3的加工。Caspase-8和Caspase-3在T细胞活化和增殖过程中被激活。caspase抑制剂可阻断CD 34 + T细胞增殖。Caspase抑制剂不能阻断T细胞增殖过程中Caspase的激活。
The caspase inhibitors, benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) and benzyloxycarbonyl (Cbz)-Ile-Glu (OMe)-Thr-Asp (OMe)-FMK (z-IETD-FMK) at non-toxic doses were found to be immunosuppressive and inhibit human T cell proliferation induced by mitogens and IL-2 in vitro. Both caspase inhibitors were shown to block NF-κB in activated primary T cells, but have little inhibitory effect on the secretion of IL-2 and IFN-γ during T cell activation. However, the expression of IL-2 receptor α-chain (CD25) in activated T cells was inhibited by both z-VAD-FMK and z-IETD-FMK, whereas the expression of the early activated T cell marker, CD69 was unaffected. During primary T cell activation via the antigen receptor, both caspase-8 and caspase-3 were activated and processed to their respective subunits, but neither caspase inhibitors had any effect on the processing of these two caspases. In sharp contrast both caspase inhibitors readily blocked apoptosis and the activation of caspases during FasL-induced apoptosis in activated primary T cells and Jurkat T cells. Collectively, the results demonstrate that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. ► Caspase-8 and caspase-3 were activated during T cell activation and proliferation. ► T cell proliferation was blocked by caspase inhibitors. ► Caspase activation during T cell proliferation was not block by caspase inhibitors.
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影响因子：
3.5
作者：
Deszcz, L;Selpelt, J;Kuechler, E
通讯作者：
Kuechler, E
影响因子：
4.8
作者：
Garcia-Calvo, M;Peterson, EP;Thornberry, NA
通讯作者：
Thornberry, NA
影响因子：
2.2
作者：
Jayaraman, S
通讯作者：
Jayaraman, S
DOI：
10.1073/pnas.93.17.8907
发表时间：
1996-08-20
影响因子：
11.1
作者：
Luo, C;Shaw, KTY;Rao, A
通讯作者：
Rao, A
影响因子：
2.2
作者：
LYONS, AB;PARISH, CR
通讯作者：
PARISH, CR