Growth hormone protects human lymphocytes from irradiation-induced cell death

Growth hormone protects human lymphocytes from irradiation-induced cell death
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DOI:
10.1038/sj.bjp.0705173
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发表时间:
2003-04-01
影响因子:
7.3
通讯作者:
Cantarella, G
Cantarella, G
中科院分区:
医学2区
文献类型:
--
作者:
Lempereur, L;Brambilla, D;Cantarella, G

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1肿瘤放射治疗的不良反应主要影响造血系统。生长激素(GH)参与造血和免疫反应的调节。我们报道了r-hGH对体外照射的人外周血淋巴细胞(PBL)的细胞死亡的预防和分泌能力的恢复。Western印迹分析表明,GH的这些作用与增加抗凋亡蛋白Bcl-2.3的表达平行,r-hGH恢复了有丝分裂原刺激的PBL释放IL-2。用生长激素受体(GHR)拮抗剂B2036和G120K预先孵育受照射的淋巴细胞,可抑制r-hGH依赖的IL-2的释放。4这些结果表明,r-hGH以一种特定的受体介导的方式保护受照射的PBL免于死亡。R-hGH对PBL的这种作用包括激活抗凋亡基因bcl2和防止细胞死亡,这与保留功能细胞的能力有关。最后,GH作为免疫增强剂在癌症放射治疗中的潜在用途是可以预见的。
1 Undesired effects of cancer radiotherapy mainly affect the hematopoietic system. Growth hormone (GH) participates in both hematopoiesis and modulation of the immune response. We report both r-hGH cell death prevention and restoration of secretory capacities of irradiated human peripheral blood lymphocytes (PBL) in vitro.2 r-hGH induced cell survival and increased proliferation of irradiated cells. Western blot analysis indicated that these effects of GH were paralleled by increased expression of the antiapoptotic protein Bcl-2.3 r-hGH restored mitogen-stimulated release of IL-2 by PBL. Preincubation of irradiated lymphocytes with the growth hormone receptor (GHR) antagonists B2036 and G120K abrogated r-hGH-dependent IL-2 release.4 These results demonstrate that r-hGH protects irradiated PBL from death in a specific, receptor-mediated manner. Such effect of r-hGH on PBL involves activation of the antiapoptotic gene bcl-2 and prevention of cell death, associated with preserved functional cell capacity. Finally, potential use of GH as an immunopotentiating agent could be envisioned during radiation therapy of cancer.