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The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages
Immunity ( IF 32.4 ) Pub Date : 2017-11-28 , DOI: 10.1016/j.immuni.2017.11.013
Charles L Evavold 1 , Jianbin Ruan 2 , Yunhao Tan 3 , Shiyu Xia 2 , Hao Wu 2 , Jonathan C Kagan 1
Affiliation  

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.



中文翻译:

毛孔形成蛋白Gasdermin D调节活巨噬细胞分泌白介素-1。

白介素-1(IL-1)家族细胞因子是胞质蛋白,在释放到细胞外空间后会表现出炎症活性。这些因子在各种细胞死亡过程后释放,而焦磷酸化是常见的机制。最近,已经认识到吞噬细胞可以达到过度激活状态,这由它们分泌IL-1的能力同时保持活力来定义,但是目前尚不清楚如何从活细胞中分泌IL-1。本文中,我们报道了热解调节剂加德敏D(GSDMD)对于已经暴露于炎性体活化剂(例如细菌及其产物或宿主衍生的氧化脂质)的活巨噬细胞分泌IL-1β是必需的。基于细胞和脂质体的测定表明,IL-1β穿过完整的脂质双层转运需要GSDMD孔。

更新日期:2017-11-28
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