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首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >Dual functionality of interleukin-1 family cytokines: implications for anti-interleukin-1 therapy
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Dual functionality of interleukin-1 family cytokines: implications for anti-interleukin-1 therapy

机译：白介素1家族细胞因子的双重功能：对抗白介素1治疗的意义

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摘要

Dysregulated inflammation contributes to disease pathogenesis in both the periphery and the brain. Cytokines are coordinators of inflammation and were originally defined as secreted mediators, released from expressing cells to activate plasma membrane receptors on responsive cells. However, a group of cytokines is now recognized as having dual functionality. In addition to their extracellular effects, these cytokines act inside the nuclei of cytokine-expressing or cytokine-responsive cells. Interleukin-1 (IL-1) family cytokines are key pro-inflammatory mediators, and blockade of the IL-1 system in inflammatory diseases is an attractive therapeutic goal. All current therapies target IL-1 extracellular actions. Here we review evidence that suggests IL-1 family members have dual functionality. Several IL-1 family members have been detected inside the nuclei of IL-1-expressing or IL-1-responsive cells, and intranuclear IL-1 is reported to regulate gene transcription and mRNA splicing. However, further work is required to determine the impact of IL-1 intranuclear actions on disease pathogenesis. The intranuclear actions of IL-1 family members represent a new and potentially important area of IL-1 biology and may have implications for the future development of anti-IL-1 therapies.
机译：炎症失调导致周围和大脑的疾病发病。细胞因子是炎症的协调者，最初被定义为分泌的介质，从表达细胞释放以激活反应性细胞上的质膜受体。但是，现在公认一组细胞因子具有双重功能。这些细胞因子除了具有细胞外作用外，还可以在表达细胞因子或细胞因子反应性细胞的细胞核内起作用。白介素-1（IL-1）家族细胞因子是关键的促炎介质，而在炎症性疾病中阻断IL-1系统是一个有吸引力的治疗目标。当前所有的疗法都针对IL-1细胞外作用。在这里，我们回顾了表明IL-1家族成员具有双重功能的证据。已在表达IL-1或IL-1反应的细胞核内检测到几个IL-1家族成员，据报道核内IL-1调节基因转录和mRNA剪接。但是，需要进一步的工作来确定IL-1核内作用对疾病发病机理的影响。 IL-1家族成员的核内作用代表了IL-1生物学的一个新的且潜在的重要领域，并且可能对抗IL-1治疗的未来发展产生影响。

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