Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis.
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DOI：
10.1084/jem.193.6.661
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发表时间：
2001-03-19
期刊：
影响因子：
--
通讯作者：
Okumura K
中科院分区：
文献类型：
--
作者：
Smyth MJ;Cretney E;Takeda K;Wiltrout RH;Sedger LM;Kayagaki N;Yagita H;Okumura K
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是由体外活化的自然杀伤细胞（NK）表达的，但这一观察结果与NK细胞的生物学功能的相关性尚不清楚。在这里，我们已经证明了小鼠TRAIL在各种组织NK细胞上的体内诱导表达，以及NK细胞活化与TRAIL介导的体内抗转移功能的相关性。TRAIL的表达仅在一部分肝脏NK细胞上构成，而先天性NK细胞对肝癌肝转移的控制部分依赖于TRAIL。给予治疗剂量的白细胞介素(IL)-12（一种NK细胞和NKT细胞产生干扰素(IFN)-γ的强效诱导剂），上调肝脏、脾脏和肺部NK细胞上TRAIL的表达，IL-12以TRAIL依赖的方式抑制肝脏和肺部的转移。相比之下，α-半乳糖神经酰胺（α-GalCer）是NKT细胞IFN-γ和IL-4分泌的强效诱导剂，可以抑制肝脏和肺转移，但仅刺激NK细胞trail介导的肝脏功能。在IFN-γ缺乏小鼠的NK细胞中未检测到TRAIL的表达，TRAIL介导的IL-12和α-GalCer的抗转移作用严格依赖于IFN-γ。这些结果表明，TRAIL对NK细胞的诱导在IFN-γ介导的IL-12和α-GalCer的抗转移作用中起关键作用。
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is expressed by in vitro activated natural killer (NK) cells, but the relevance of this observation to the biological function of NK cells has been unclear. Herein, we have demonstrated the in vivo induction of mouse TRAIL expression on various tissue NK cells and correlated NK cell activation with TRAIL-mediated antimetastatic function in vivo. Expression of TRAIL was only constitutive on a subset of liver NK cells, and innate NK cell control of Renca carcinoma hepatic metastases in the liver was partially TRAIL dependent. Administration of therapeutic doses of interleukin (IL)-12, a powerful inducer of interferon (IFN)-γ production by NK cells and NKT cells, upregulated TRAIL expression on liver, spleen, and lung NK cells, and IL-12 suppressed metastases in both liver and lung in a TRAIL-dependent fashion. By contrast, α-galactosylceramide (α-GalCer), a powerful inducer of NKT cell IFN-γ and IL-4 secretion, suppressed both liver and lung metastases but only stimulated NK cell TRAIL-mediated function in the liver. TRAIL expression was not detected on NK cells from IFN-γ–deficient mice and TRAIL-mediated antimetastatic effects of IL-12 and α-GalCer were strictly IFN-γ dependent. These results indicated that TRAIL induction on NK cells plays a critical role in IFN-γ–mediated antimetastatic effects of IL-12 and α-GalCer.
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影响因子：
32.4
作者：
DIGHE, AS;RICHARDS, E;SCHREIBER, RD
通讯作者：
SCHREIBER, RD
DOI：
10.1084/jem.190.8.1155
发表时间：
1999-10-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fanger NA;Maliszewski CR;Schooley K;Griffith TS
通讯作者：
Griffith TS
影响因子：
4.4
作者：
GATELY, MK;WARRIER, RR;MURPHY, M
通讯作者：
MURPHY, M
影响因子：
5.3
作者：
Gibson, SB;Oyer, R;Johnson, GL
通讯作者：
Johnson, GL
影响因子：
9.2
作者：
Marsters, SA;Sheridan, JP;Ashkenazi, A
通讯作者：
Ashkenazi, A