Evavold Charles L, Kagan Jonathan C
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States.
Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.
Front Cell Dev Biol. 2022 Jun 27;10:910983. doi: 10.3389/fcell.2022.910983. eCollection 2022.
The majority of interleukin-1 (IL-1) family cytokines lack amino terminal secretion signals or transmembrane domains for secretion along the conventional biosynthetic pathway. Yet, these factors must be translocated from the cytoplasm across the plasma membrane into the extracellular space in order to regulate inflammation. Recent work has identified an array of mechanisms by which IL-1 family cytokines can be released into the extracellular space, with supramolecular organizing centers known as inflammasomes serving as dominant drivers of this process. In this review, we discuss current knowledge of the mechanisms of IL-1 family cytokine synthesis, processing, and release from cells. Using this knowledge, we propose a model whereby host metabolic state dictates the route of IL-1β secretion, with implications for microbial infection and sterile inflammation.
大多数白细胞介素-1（IL-1）家族细胞因子缺乏氨基末端分泌信号或跨膜结构域，无法沿传统生物合成途径分泌。然而，这些因子必须从细胞质穿过质膜转运到细胞外空间，以调节炎症。最近的研究发现了一系列机制，通过这些机制，IL-1家族细胞因子可以释放到细胞外空间，其中作为超分子组织中心的炎性小体是这一过程的主要驱动因素。在这篇综述中，我们讨论了目前关于IL-1家族细胞因子合成、加工和从细胞中释放机制的知识。利用这些知识，我们提出了一个模型，即宿主代谢状态决定IL-1β的分泌途径，这对微生物感染和无菌性炎症具有重要意义。
