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首页> 外文期刊>Journal of endotoxin research >Endotoxin signaling in human macrophages: signaling via an alternate mechanism.
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Endotoxin signaling in human macrophages: signaling via an alternate mechanism.

机译:人类巨噬细胞中的内毒素信号传导:通过另一种机制的信号传导。

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摘要

Lipopolysaccharide (LPS) signals through Toll-like receptors (TLRs) in the course of sepsis, resulting in the release of inflammatory factors. In cell lines and murine models, parts of the signaling pathways involved have been elucidated with MyD88, Mal/TIRAP and IKK2 playing an important role in the induction of NF-kappaB. By focusing on primary human cells, we have shown that there are fundamental signaling differences between human and murine macrophages and between cells of myeloid and non-myeloid origins. In primary human cells, there are no available knockouts so we employed the use of dominant negatives to investigate the signaling cascades. We show that in primary human macrophages MyD88, Mal/TIRAP and IKK2-independent alternative pathways activate NF-kappaB and induce the expression of inflammatory cytokines, whereas in non-myeloid synovial fibroblasts MyD88 and/or Mal/TIRAP are essential adaptors for LPS signaling.
机译:脂多糖(LPS)在败血症过程中通过Toll样受体(TLR)发出信号,导致炎症因子释放。在细胞系和鼠模型中,已经阐明了涉及的部分信号通路,其中MyD88,Mal / TIRAP和IKK2在诱导NF-κB中起重要作用。通过关注人类原代细胞,我们已经表明,人类和鼠巨噬细胞之间以及髓系和非髓系起源的细胞之间存在基本的信号差异。在原代人类细胞中,没有可用的基因敲除,因此我们采用了显性阴性来研究信号级联反应。我们显示,在主要的人类巨噬细胞MyD88中,Mal / TIRAP和IKK2独立的替代途径激活NF-κB并诱导炎性细胞因子的表达,而在非髓样滑膜成纤维细胞中,MyD88和/或Mal / TIRAP是LPS信号转导的必不可少的适配器。

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