Interleukin-33 signaling
中文名称
通路描述
IL33 是一种 Interlukin-1 家族的细胞因子。它被分类为alarmin，因为它是在细胞损伤时释放到细胞外空间的。它作为一种内源性危险信号发挥作用(Liew et al. 2010)。该基因产物具有生物活性（全长 IL33）。其效力据报道在炎症蛋白酶如 Cathepsin G(CTSG) 和中性粒细胞弹性蛋白酶(ELANE) 在 N 端进行切割后显著增加（高达 30 倍）(Lefrançais et al. 2012, Lefrançais et al. 2014)，但其他人认为加工会无活性(Cayrol & Girard 2009)。IL33 可以作为细胞外配体和细胞内信号分子(Martin et al. 2013, 2016)。全长 IL33 具有核定位序列，可以转位到细胞核内，在那里它与异染色质结合(Moussion et al. 2008, Carriere et al. 2007, Roussel et al. 2008, Kuchler et al. 2008, Sundlisaeter et al. 2012, Baekkevold et al. 2003)。经过蛋白酶解加工的 IL33 无法转位到细胞核内(Martin et al. 2013, Ali et al. 2010)。细胞外 IL33 与其受体 Interleukin-1 受体类似蛋白 1(IL1RL1, 抑制肿瘤生成 2, ST2) 的结合启动几种细胞信号通路。细胞损伤或死亡是 IL33 到达细胞外环境的主要机制，IL33 不是由细胞主动分泌的(Martin et al. 2016, Kaczmarek et al. 2013, Vancamelbeke et al. 2017)。由于 IL33 由内皮细胞和上皮细胞组成型表达，因此在细胞损伤和坏死后立即可到达细胞外微环境(Lefrançais et al. 2012)。细胞外 ATP 或机械压力的增加与肥大细胞或心肌细胞分别增加 IL33 分泌相关(Shimokawa et al. 2017, Kakkar et al. 2012, Zhao et al. 2012, Sanada et al. 2007, Chen et al. 2015)。可溶性 IL1RL1(IL1RL1 异构体 C, ST2V) (Iwahana et al. 2005, Tominaga et al. 1999) 共享 IL1RL1 的细胞外成分，包括配体结合域，但缺乏 IL1RL1 的跨膜和细胞内成分(Kakkar et al. 2008, Iwahana et al. 1999)。IL33-IL1RL1 复合物招募一个共受体，最常见的是 IL1 受体辅助蛋白(IL1RAP, IL-1RAcP)(Schmitz et al. 2005, Lingel et al. 2009, Palmer et al. 2008, Liu et al. 2013)。
英文描述
Interleukin-33 signaling Interleukin-33 (IL33) cytokine is a member of the Interleukin-1 family. It can be classified as an alarmin because it is released into the extracellular space during cell damage. It acts as an endogenous danger signal (Liew et al. 2010).] The gene product is biologically active (full-length IL33). Its potency has been reported to increase significantly (up to 30x) after cleavage at the N-terminus by inflammatory proteases such as Cathepsin G (CTSG) and Neutrophil elastase (ELANE) (Lefrançais et al. 2012, Lefrançais et al. 2014) but others have suggested that processing inactivates IL33 (Cayrol & Girard 2009). IL33 can act as an extracellular ligand and an intracellular signaling molecule (Martin et al. 2013, 2016). Full-length IL33 has a nuclear localization sequence and can translocate to the nucleus, where it binds heterochromatin (Moussion et al. 2008, Carriere et al. 2007, Roussel et al. 2008, Kuchler et al. 2008, Sundlisaeter et al. 2012, Baekkevold et al. 2003). IL33 that has undergone proteolytic processing is unable to translocate to the nucleus (Martin et al. 2013, Ali et al. 2010). Binding of extracellular IL33 to its receptor Interleukin-1 receptor-like 1 (IL1RL1, suppression of tumorigenicity 2, ST2) initiates several cellular signaling pathways. Cell injury or death are the dominant mechanisms by which IL33 reaches the extracellular environment, IL33 is not actively secreted by cells (Martin et al. 2016, Kaczmarek et al. 2013, Vancamelbeke et al. 2017). Because IL33 is expressed constitutively by endothelial and epithelial cells it is immediately available to the extracellular microenvironment after cell injury and necrosis (Lefrançais et al. 2012). Increases in extracellular ATP or mechanical stress correlate with increased IL33 secretion by mast cells or cardiomyocytes, respectively (Shimokawa et al. 2017, Kakkar et al. 2012, Zhao et al. 2012, Sanada et al. 2007, Chen et al. 2015). Soluble IL1RL1 (IL1RL1 Isoform C, ST2V) (Iwahana et al. 2005, Tominaga et al. 1999) shares the extracellular components of IL1RL1, including the ligand binding domain, but lacks the transmembrane and intracellular components of IL1RL1 (Kakkar et al. 2008, Iwahana et al. 1999). The IL33-IL1RL1 complex recruits a co-receptor, most commonly IL1 receptor accessory protein (IL1RAP, IL-1RAcP) (Schmitz et al. 2005, Lingel et al. 2009, Palmer et al. 2008, Liu et al. 2013).
所含基因
2 个基因