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首页> 外文期刊>Cellular immunology >Sequential activation of inflammatory signaling pathways during graft-versus-host disease (GVHD): early role for STAT1 and STAT3.
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Sequential activation of inflammatory signaling pathways during graft-versus-host disease (GVHD): early role for STAT1 and STAT3.

机译:移植物抗宿主病(GVHD)期间炎症信号通路的顺序激活:STAT1和STAT3的早期作用。

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摘要

The aim of this study was to delineate the temporal and spatial sequence of STAT1 and STAT3 activation during development of GVHD following fully Major Histocompatibility Complex (MHC)-mismatched allogeneic Bone Marrow Transplantation (BMT). Activation of inflammatory signaling pathways in GVHD target organs was assessed by western blotting, phospho-flow cytometry and electromobility shift assays (EMSA). Development of GVHD was associated with significant expansion of phospho[p]-STAT1 and p-STAT3 expressing CD4(+) T cells and CD8(+) T cells. GVHD-specific STAT3/STAT1 activation preceded activation of Nuclear Factor-kappaB (NF-kappaB) and Mitogen Activated Protein Kinase (MAPK) and was associated with subsequent induction of STAT1 or STAT3-dependent inflammatory gene-expression programs (e.g. expression of IRF-1, SOCS1, IL-17). Our studies may help to establish a functional hierarchy of the signaling events leading to the development of GVHD and could be helpful in designing new molecularly targeted treatment approaches for GVHD.
机译:这项研究的目的是描绘在完全主要组织相容性复合体(MHC)不匹配的同种异体骨髓移植(BMT)后GVHD发生期间STAT1和STAT3激活的时间和空间序列。通过蛋白质印迹,磷酸流式细胞仪和电动迁移率分析(EMSA)评估了GVHD目标器官中炎症信号通路的激活。 GVHD的发展与表达磷酸化[p] -STAT1和p-STAT3的CD4(+)T细胞和CD8(+)T细胞的显着扩增有关。 GVHD特异性的STAT3 / STAT1激活先于核因子-κB(NF-kappaB)和丝裂原活化的蛋白激酶(MAPK)的激活,并且与随后诱导STAT1或STAT3依赖性炎症基因表达程序(例如IRF- 1,SOCS1,IL-17)。我们的研究可能有助于建立导致GVHD发生的信号事件的功能层次,并可能有助于设计GVHD的新型分子靶向治疗方法。

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