首页> 外文期刊>American Journal of Physiology >High mobility group box 1 protein interacts with multiple Toll-like receptors.
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High mobility group box 1 protein interacts with multiple Toll-like receptors.

机译:高迁移率的第1组框蛋白与多种Toll样受体相互作用。

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摘要

High mobility group box 1 (HMGB1), originally described as a DNA-binding protein, can also be released extracellularly and functions as a late mediator of inflammatory responses. Although recent reports have indicated that the receptor for advanced glycation end products (RAGE) as well as Toll-like receptor (TLR)2 and TLR4 are involved in cellular activation by HMGB1, there has been little evidence of direct association between HMGB1 and these receptors. To examine this issue, we used fluorescence resonance energy transfer (FRET) and immunoprecipitation to directly investigate cell surface interactions of HMGB1 with TLR2, TLR4, and RAGE. FRET images in RAW264.7 macrophages demonstrated association of HMGB1 with TLR2 and TLR4 but not RAGE. Transient transfections into human embryonic kidney-293 cells showed that HMGB1 induced cellular activation and NF-kappaB-dependent transcription through TLR2 or TLR4 but not RAGE. Coimmunoprecipitation also found interaction between HMGB1 and TLR2 as well as TLR4, but not with RAGE. These studies provide the first direct evidence that HMGB1 can interact with both TLR2 and TLR4 and also supply an explanation for the ability of HMGB1 to induce cellular activation and generate inflammatory responses that are similar to those initiated by LPS.
机译:高迁移率族盒1(HMGB1),最初被描述为DNA结合蛋白,也可以在细胞外释放,并起炎症反应的晚期介体的作用。尽管最近的报道表明,高级糖基化终产物(RAGE)的受体以及Toll样受体(TLR)2和TLR4参与了HMGB1的细胞激活,但几乎没有证据表明HMGB1与这些受体之间存在直接联系。要检查此问题,我们使用了荧光共振能量转移(FRET)和免疫沉淀法来直接研究HMGB1与TLR2,TLR4和RAGE的细胞表面相互作用。 RAW264.7巨噬细胞中的FRET图像显示HMGB1与TLR2和TLR4相关,但与RAGE无关联。瞬时转染到人类胚胎肾293细胞中表明HMGB1通过TLR2或TLR4而非RAGE诱导细胞活化和NF-κB依赖性转录。免疫共沉淀还发现了HMGB1和TLR2以及TLR4之间的相互作用,但未与RAGE相互作用。这些研究为HMGB1可以与TLR2和TLR4相互作用提供了第一个直接证据,也为HMGB1诱导细胞激活并产生类似于LPS引发的炎症反应的能力提供了解释。

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