The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages.
The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages.
复制标题
形成孔的蛋白质加油D可以调节白细胞介素-1的巨噬细胞分泌。
DOI：
10.1016/j.immuni.2017.11.013
复制
发表时间：
2018-01-16
期刊：
影响因子：
32.4
通讯作者：
Kagan JC
中科院分区：
文献类型：
--
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
白细胞介素-1（IL-1）家族细胞因子是胞质蛋白，其在释放到细胞外空间时表现出炎症活性。这些因子在各种细胞死亡过程后释放，其中火亡是一种常见机制。最近，人们认识到，吞噬细胞可以达到超活化状态，这是由它们分泌IL-1同时保持活力的能力定义的，但还不清楚IL-1如何从活细胞中分泌。在本文中，我们报告了焦亡调节剂gasdermin D（GSDMD）是暴露于炎性体激活剂（如细菌及其产物或宿主来源的氧化脂质）的活巨噬细胞分泌IL-1β所必需的。基于细胞和脂质体的测定表明，GSDMD孔是IL-1β跨完整脂质双层转运所必需的。这些发现确定了GSDMD的非pyroptotic功能，并提出了GSDMD孔代表细胞超活化条件下分泌胞质细胞因子的管道的可能性。炎性小体引起细胞凋亡或细胞过度活化，后者被定义为释放IL-1的活细胞。Evavold等报道，成孔蛋白gasdermin D调节过度活跃的巨噬细胞释放IL-1。基于细胞和脂质体的测定显示，gasdermin D孔允许IL-1穿过完整的脂质双层。
The Interleukin-1 (IL-1) family cytokines are cytosolic proteins that exhibit inflammatory activity upon release into the extracellular space. These factors are released following various cell death processes, with pyroptosis being a common mechanism. Recently, it was recognized that phagocytes can achieve a state of hyperactivation, which is defined by their ability to secrete IL-1 while retaining viability, yet it is unclear how IL-1 can be secreted from living cells. Herein, we report that the pyroptosis regulator gasdermin D (GSDMD) was necessary for IL-1β secretion from living macrophages that have been exposed to inflammasome activators, such as bacteria and their products or host-derived oxidized lipids. Cell- and liposome-based assays demonstrated that GSDMD pores were required for IL-1β transport across an intact lipid bilayer. These findings identify a non-pyroptotic function for GSDMD, and raise the possibility that GSDMD pores represent conduits for the secretion of cytosolic cytokines under conditions of cell hyperactivation. Inflammasomes elicit pyroptosis or cell hyperactivation, with the latter defined as living cells that release IL-1. Evavold et al report that the pore-forming protein gasdermin D regulates IL-1 release from hyperactive macrophages. Cell- and liposome-based assays revealed that gasdermin D pores permit IL-1 passage across intact lipid bilayers.
登录
查看更多内容
影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
影响因子：
8.8
作者：
Tzeng TC;Schattgen S;Monks B;Wang D;Cerny A;Latz E;Fitzgerald K;Golenbock DT
通讯作者：
Golenbock DT
Interleukin-1家族：回到未来。
影响因子：
32.4
作者：
Garlanda C;Dinarello CA;Mantovani A
通讯作者：
Mantovani A
DOI：
10.1126/science.aaf3036
发表时间：
2016-06-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zanoni I;Tan Y;Di Gioia M;Broggi A;Ruan J;Shi J;Donado CA;Shao F;Wu H;Springstead JR;Kagan JC
通讯作者：
Kagan JC
影响因子：
64.8
作者：
Shi, Jianjin;Zhao, Yue;Shao, Feng
通讯作者：
Shao, Feng