...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cytokine >Melphalan exposure induces an interleukin-6 deficit in bone marrow stromal cells and osteoblasts
【24h】

Melphalan exposure induces an interleukin-6 deficit in bone marrow stromal cells and osteoblasts

机译：Melphalan暴露诱导骨髓基质细胞和成骨细胞中白介素6缺乏

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bone marrow stromal cells (BMSC) and osteoblasts are critical components of the microenvironment that support hematopoietic recovery following bone marrow transplantation. Aggressive chemotherapy not only affects tumor cells, but also influences additional structural and functional components of the microenvironment. Successful reconstitution of hematopoiesis following stem cell or bone marrow transplantation after aggressive chemotherapy is dependent upon components of the microenvironment maintaining their supportive function. This includes secretion of soluble factors and expression of cellular adhesion molecules that impact on development of hematopoietic cells. In the current study, we investigated the effects of chemotherapy treatment on BMSC and human osteoblast (HOB) expression of interleukin-6 (IL-6) as one regulatory factor.IL-6 is a pleiotropic cytokine which has diverse effects on hematopoietic cell development. In the current study we demonstrate that exposure of BMSC or HOB to melphalan leads to decreases in IL-6 protein expression. Decreased IL-6 protein is the most pronounced following melphalan exposure compared to several other chemotherapeutic agents tested. We also observed that melphalan decreased IL-6 mRNA in both BMSC and HOB. Finally, using a model of BMSC or HOB co-cultured with myeloma cells exposed to melphalan, we observed that IL-6 protein was also decreased, consistent with treatment of adherent cells alone. Collectively, these observations are of dual significance. First, suggesting that chemotherapy induced IL-6 deficits in the bone marrow occur which may result in defective hematopoietic support of early progenitor cells. In contrast, the decrease in IL-6 protein may be a beneficial mechanism by which melphalan acts as a valuable therapeutic agent for treatment of multiple myeloma, where IL-6 present in the bone marrow acts as a proliferative factor and contributes to disease progression. Taken together, these data emphasize the responsiveness of the microenvironment to diverse stress that is important to consider in therapeutic settings.
机译：骨髓基质细胞（BMSC）和成骨细胞是支持骨髓移植后造血功能恢复的微环境的关键组成部分。积极的化学疗法不仅影响肿瘤细胞，而且影响微环境的其他结构和功能组件。积极化疗后干细胞或骨髓移植后造血功能的成功重建取决于维持其支持功能的微环境成分。这包括可溶性因子的分泌和影响造血细胞发育的细胞粘附分子的表达。在本研究中，我们研究了化疗对BMSC和白细胞介素6（IL-6）作为一种调节因子的人成骨细胞（HOB）表达的影响.IL-6是一种多效性细胞因子，对造血细胞的发育具有多种作用。在当前的研究中，我们证明BMSC或HOB暴露于美法仑导致IL-6蛋白表达降低。与测试的其他几种化疗药物相比，美法仑暴露后IL-6蛋白的减少最为明显。我们还观察到美法仑降低了BMSC和HOB中的IL-6 mRNA。最后，使用与暴露于美法仑的骨髓瘤细胞共培养的BMSC或HOB模型，我们观察到IL-6蛋白也降低，与单独处理贴壁细胞一致。总而言之，这些观察具有双重意义。首先，提示化学疗法诱导的骨髓中IL-6缺乏发生，这可能导致早期祖细胞的造血支持不足。相反，IL-6蛋白的减少可能是有益的机制，美法仑可通过该机制而成为治疗多发性骨髓瘤的有价值的治疗剂，其中骨髓中的IL-6充当增殖因子并促进疾病进展。综上所述，这些数据强调了微环境对多种压力的反应性，这在治疗环境中必须加以考虑。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号