IL-1 加工
中文名称
通路描述
与类型 1 IL-1R 作用的 IL-1 家族细胞因子包括 IL-1α (IL1A)、IL-1β (IL1B) 和 IL-1 受体拮抗蛋白 (IL1RAP)。IL1RAP 含有信号肽并通过经典分泌途径以成熟蛋白形式分泌。IL1A 和 IL1B 在激活细胞中以胞质前体 (pro-IL1A 和 pro-IL1B) 形式合成，它们没有信号序列，因此不能通过经典的 ER-Golgi 途径分泌。pro-IL1B 加工为活性形式需要 caspase-1 (Thornberry et al. 1992)，而 caspase-1 本身是由称为 inflammasome 的分子支架激活的。IL1B 的加工和释放被认为密切相关，因为成熟的 IL1B 仅在炎症细胞内释放前才能被观察到。据报道，在单核细胞中，部分细胞 IL1B 是通过晚期内体和早期溶酶体的调节性分泌释放的，这可能代表一个细胞内腔，其中 pro-IL1B 的 caspase-1 加工发生。从细胞膜微囊泡的脱落也被认为是分泌机制之一 (MacKenzie et al. 2001)。这些提议取代了先前认为由于细胞裂解和非特异性释放通过细胞膜孔道而发生的模型。然而，文献中支持所有这些机制的证据仍然存在，关于 IL1B 如何从细胞中出仍有争议 (Brough & Rothwell 2007)。据报道，一种钙蛋白酶对于 pro-IL1A 的加工很重要，但关于 IL1A 如何从细胞中释放以及它在生物学中具体发挥什么作用知之甚少。
英文描述
Interleukin-1 processing The IL-1 family of cytokines that interact with the Type 1 IL-1R include IL-1α (IL1A), IL-1β (IL1B) and the IL-1 receptor antagonist protein (IL1RAP). IL1RAP is synthesized with a signal peptide and secreted as a mature protein via the classical secretory pathway. IL1A and IL1B are synthesised as cytoplasmic precursors (pro-IL1A and pro-IL1B) in activated cells. They have no signal sequence, precluding secretion via the classical ER-Golgi route (Rubartelli et al. 1990). Processing of pro-IL1B to the active form requires caspase-1 (Thornberry et al. 1992), which is itself activated by a molecular scaffold termed the inflammasome (Martinon et al. 2002). Processing and release of IL1B are thought to be closely linked, because mature IL1B is only seen inside inflammatory cells just prior to release (Brough et al. 2003). It has been reported that in monocytes a fraction of cellular IL1B is released by the regulated secretion of late endosomes and early lysosomes, and that this may represent a cellular compartment where caspase-1 processing of pro-IL1B takes place (Andrei et al. 1999). Shedding of microvesicles from the plasma membrane has also been proposed as a mechanism of secretion (MacKenzie et al. 2001). These proposals superceded previous models in which non-specific release due to cell lysis and passage through a plasma membrane pore were considered. However, there is evidence in the literature that supports all of these mechanisms and there is still controversy over how IL1B exits from cells (Brough & Rothwell 2007). A calpain-like potease has been reported to be important for the processing of pro-IL1A, but much less is known about how IL1A is released from cells and what specific roles it plays in biology.
所含基因
9 个基因