...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury
【24h】

Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury

机译：白细胞介素1受体拮抗剂介导间充质干细胞在肺损伤中的抗炎和抗纤维化作用

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

Mesenchymal stem cells (MSCs) have been exploited as cellular vectors to treat a wide array of diseases but the mechanisms responsible for their therapeutic effect remain indeterminate. Previously, we reported that MSCs inhibit bleomycin (BLM)-induced inflammation and fibrosis within the lungs of mice. Interrogation of the MSCtranscriptome identified interleukin 1 receptor antagonist (IL1RN) as a potential mediator of this effect. Fraction-ation studies indicated that MSCs are the principal source of IL1RN in murine bone marrow and that its expression is restricted to a unique subpopulation of cells. Moreover, MSC-conditioned media was shown to block proliferation of an IL-1α-dependent T cell line and inhibit production of TNF-α by activated macrophages in vitro. Studies conducted in mice revealed that MSC administration was more effective than recombinant IL1RN delivered via adenoviral infection or osmotic pumps in inhibiting BLM-induced increases in TNF-α, IL-1α, and IL1RN mRNA in lung, IL1RN protein in bronchoal-veolar lavage (BAL) fluid, and trafficking of lymphocytes and neutrophils into the lung. Therefore, MSCs protect lung tissue from BLM-induced injury by blocking TNF-α and IL-1, two fundamental proinflammatory cytokines in lung. Identification of IL1RN-expressing human MSC subpopulations may provide a novel cellular vector for treating chronic inflammatory diseases in humans.
机译：间充质干细胞（MSCs）已被用作治疗多种疾病的细胞载体，但对其治疗效果负责的机制仍不确定。以前，我们报道了MSC可抑制博莱霉素（BLM）诱导的小鼠肺部炎症和纤维化。对MSC转录组的询问确定白介素1受体拮抗剂（IL1RN）是这种作用的潜在介体。分馏研究表明，MSC是鼠骨髓中IL1RN的主要来源，其表达仅限于细胞的独特亚群。此外，MSC条件培养基显示在体外可阻断IL-1α依赖性T细胞系的增殖并抑制活化巨噬细胞产生TNF-α。在小鼠中进行的研究表明，与通过腺病毒感染或渗透泵输送的重组IL1RN相比，MSC抑制BLM诱导的肺中TNF-α，IL-1α和IL1RN mRNA的增加，支气管肺泡灌洗中IL1RN蛋白的增加更有效（ BAL）液，以及淋巴细胞和中性粒细胞向肺的运输。因此，MSC通过阻断TNF-α和IL-1（肺中两种基本的促炎细胞因子）来保护肺组织免受BLM诱导的损伤。鉴定表达IL1RN的人MSC亚群可以提供一种用于治疗人的慢性炎性疾病的新型细胞载体。

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