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Inflammasome-Independent Regulation of IL-1-Family Cytokines

机译:IL-1家族细胞因子的炎症独立调节

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Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the exception of the IL-1 receptor antagonist, all IL-1 family cytokines lack a signal peptide and require proteolvtic processing into an active molecule. One such unique protease is caspase-1, which is activated by protein platforms called the inflammasomes. However, increasing evidence suggests that inflasomes and caspase-1 are not the only mechanism for processing IL-1 cytokines. IL-1 cytokines are often released as precursors and require extracellular processing for activity. Here we review the inflammasome-independent enzymatic processes that are able to activate IL-1 cytokines, paying special attention to neutrophil-derived serine proteases, which subsequently induce inflammation and modulate host defense. The inflammasome-independent processing of IL-1 cytokines has important consequences for understanding inflammatory diseases, and it impacts the design of IL-1-based modulatory therapies.
机译:促炎细胞因子的诱导,生产和释放是建立有效主体防御的必要步骤。白细胞介素-11(IL-1)家族的细胞因子诱发炎症并调节T淋巴细胞反应,同时表现出稳态和代谢活动。除了IL-1受体拮抗剂外,所有IL-1家族细胞因子缺乏信号肽,并需要蛋白质醇加工成活性分子。一种这样的独特蛋白酶是Caspase-1,其被称为炎症的蛋白质平台激活。然而,越来越多的证据表明,血液酶和Caspase-1不是加工IL-1细胞因子的唯一机制。 IL-1细胞因子通常被释放为前体,并且需要用于活动的细胞外加工。在这里,我们审查了能够激活IL-1细胞因子的炎症组合的酶法,特别注意中性粒细胞衍生的丝氨酸蛋白酶,其随后诱导炎症和调节宿主防御。 IL-1细胞因子的炎症性无关加工对了解炎症性疾病具有重要影响,并且它会影响IL-1的调节疗法的设计。

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