Molecular Cell Biology Laboratory, Dept. of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
Molecular Cell Biology Laboratory, Dept. of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
Cytokine. 2022 Sep;157:155935. doi: 10.1016/j.cyto.2022.155935. Epub 2022 Jun 24.
Members of the extended IL-1 cytokine family play key roles as instigators of inflammation in numerous infectious and sterile injury contexts and are highly enriched at barrier surfaces such as the skin, lungs and intestinal mucosa. Because IL-1 family cytokines do not possess conventional ER-golgi trafficking and secretory signals, these cytokines are typically released into the extracellular space due to tissue damage resulting in necrosis, or pathogen detection resulting in pyroptosis. The latter feature, in combination with other factors, suggests that IL-1 family cytokines serve as canonical damage-associated molecular patterns (DAMPs), which instigate inflammation in response to tissue damage. However, IL-1 family cytokines also require a proteolytic activation step and diverse intracellular, extracellular and non-self proteases have been identified that are capable of processing and activating members of this family. This suggests that IL-1 family members function as sentinels for aberrant protease activity, which is frequently associated with infection or tissue damage. Here, we overview the diversity of proteases implicated in the activation of IL-1 family cytokines and suggest that this ancient cytokine family may have evolved to complement 'pattern recognition receptors', by serving as 'activity recognition receptors' enabling the detection of aberrant enzyme activity indicative of 'danger'.
白细胞介素-1（IL-1）细胞因子家族的成员在许多感染和无菌性损伤的情况下作为炎症的启动因子发挥着关键作用，并且在皮肤、肺部和肠道黏膜等屏障表面高度富集。由于 IL-1 家族细胞因子不具有传统的内质网-高尔基体运输和分泌信号，这些细胞因子通常由于组织坏死导致的细胞损伤或由于病原体检测导致的细胞焦亡而释放到细胞外空间。后一特征与其他因素一起表明，IL-1 家族细胞因子作为经典的损伤相关分子模式（DAMPs），在组织损伤时引发炎症。然而，IL-1 家族细胞因子还需要一个蛋白水解激活步骤，并且已经鉴定出多种细胞内、细胞外和非自身的蛋白酶，它们能够加工和激活该家族的成员。这表明 IL-1 家族成员作为异常蛋白酶活性的哨兵发挥作用，异常蛋白酶活性通常与感染或组织损伤有关。在这里，我们概述了参与白细胞介素-1 细胞因子激活的蛋白酶的多样性，并提出这个古老的细胞因子家族可能已经进化为补充“模式识别受体”，作为“活性识别受体”，能够检测到表明“危险”的异常酶活性。
