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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dose-dependent cross-talk between the transforming growth factor-β and interleukin-1 signaling pathways
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Dose-dependent cross-talk between the transforming growth factor-β and interleukin-1 signaling pathways

机译：转化生长因子-β和白介素-1信号通路之间的剂量依赖性串扰

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Some tumor cell lines secrete high concentrations of TGFβ or IL-1, Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGFβ activates NFκB, and IL-1β activates Smads. The IL-1 signaling components IRAK, MyD88, TRAF6, and TAK1 are all required for cross-activation of NFκB by TGFβ. Knockdown experiments revealed that both TGFβ receptor subunits are required for IL-1β to activate Smads, and the IL-1 receptor is required for TGFβ to activate NFκB. Coimmunoprecipitations showed that either TGFβ or IL-1β stimulate ligand-dependent association of all three receptor subunits. Furthermore, cross-talk between the TGFβ and IL-1 signaling pathways leads to dose-dependent cross-control of gene expression. These interactions provide new insight into biological responses to IL-1 and TGFβ in the proximity of tumors that secrete high concentrations of these factors and probably also at sites of inflammation, where the local concentrations of these cytokines are likely to be high.
机译：一些肿瘤细胞系分泌高浓度的TGFβ或IL-1，类似地，每种细胞因子的高浓度也会交叉激活另一条途径：TGFβ激活NFκB，IL-1β激活Smads。 TGFβ对NFκB的交叉激活均需要IL-1信号成分IRAK，MyD88，TRAF6和TAK1。击倒实验表明，IL-1β激活Smads需要两个TGFβ受体亚基，而TGFβ激活NFκB需要IL-1受体。免疫共沉淀显示，TGFβ或IL-1β均可刺激所有三个受体亚基的配体依赖性缔合。此外，TGFβ和IL-1信号通路之间的串扰导致基因表达的剂量依赖性交叉控制。这些相互作用为分泌高浓度这些因子的肿瘤附近以及可能在炎症部位（这些细胞因子的局部浓度可能很高）的肿瘤附近对IL-1和TGFβ的生物学反应提供了新的见识。

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