Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.
Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.
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DOI：
10.1371/journal.pone.0110748
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ohdan H
中科院分区：
文献类型：
--
作者：
Dang VT;Tanabe K;Tanaka Y;Tokumoto N;Misumi T;Saeki Y;Fujikuni N;Ohdan H
临床实践中经常观察到的急性饥饿有时会增强自然杀伤细胞对肿瘤细胞的细胞溶解活性。在这项研究中，我们研究了小鼠禁食增强自然杀伤细胞功能的分子机制。从C57 BL/6 J小鼠获得的单位重量的肝组织中的肝驻留自然杀伤细胞的总数在禁食3天后没有变化，而肿瘤坏死因子相关凋亡诱导配体（TRAIL）+和CD 69+自然杀伤细胞的比例显著升高（n = 7，p <0.01），如通过流式细胞术分析测定的。 此外，我们发现，过继转移到Rag-2−/− γ链−/−小鼠中的TRAIL−自然杀伤细胞在禁食小鼠中转化为TRAIL+自然杀伤细胞的比例高于进食小鼠。禁食3天后，肝脏自然杀伤细胞也表现出较高的TRAIL介导的抗肿瘤功能。由于这些禁食小鼠在肝组织中高度表达热休克蛋白70（n = 7，p <0.05），如通过蛋白质印迹所测定的，因此研究了该蛋白质在自然杀伤细胞活化中的作用。 用50 μg/mL重组热休克蛋白70处理肝淋巴细胞导致肝自然杀伤细胞中TRAIL和CD 69的上调（n = 6，p <0.05）。 此外，通过在禁食前向小鼠腹腔内注射抗热休克蛋白70单克隆抗体来中和HSP 70导致TRAIL表达下调（n = 6，p <0.05）。 这些发现表明，急性禁食通过上调热休克蛋白70增强TRAIL介导的肝脏自然杀伤细胞对肿瘤细胞的活性。
Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)+ and CD69+ natural killer cells were significantly elevated (n = 7, p <0.01), as determined by flow cytometric analysis. Furthermore, we found that TRAIL− natural killer cells that were adoptively transferred into Rag-2−/− γ chain−/− mice could convert into TRAIL+ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05) in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05). In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05). These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.
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DOI：
10.4049/jimmunol.1201837
发表时间：
2013-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Clinthorne JF;Beli E;Duriancik DM;Gardner EM
通讯作者：
Gardner EM
影响因子：
4.4
作者：
Elsner, Leslie;Muppala, Vijayakumar;Dressel, Ralf
通讯作者：
Dressel, Ralf
影响因子：
5.4
作者：
KIESSLING, R;KLEIN, E;WIGZELL, H
通讯作者：
WIGZELL, H
DOI：
10.1084/jem.193.6.661
发表时间：
2001-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Smyth MJ;Cretney E;Takeda K;Wiltrout RH;Sedger LM;Kayagaki N;Yagita H;Okumura K
通讯作者：
Okumura K
影响因子：
13.5
作者：
Ochi, M;Ohdan, H;Asahara, T
通讯作者：
Asahara, T