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K+ regulates relocation of Pellino-2 to the site of NLRP3 inflammasome activation in macrophages
FEBS Letters ( IF 3.5 ) Pub Date : 2021-08-13 , DOI: 10.1002/1873-3468.14176
Ileana Cristea 1 , Ove Bruland 2 , Eyvind Rødahl 1, 3 , Cecilie Bredrup 1, 3
Affiliation  

Pellino proteins are E3 ubiquitin ligases involved in the innate immune system. Recently, Pellino-2 was reported to modulate the activation of the mouse Nlrp3 inflammasome. We examined the intracellular localization of human Pellino-2 in THP1-derived macrophages during activation with LPS and ATP. We observed that Pellino-2 changed intracellular localization and colocalized with the inflammasome proteins NLRP3 and ASC late in the assembly of the inflammasome. Colocalization with NLRP3 and ASC was also seen in cells maintained in potassium-free medium. The colocalization and inflammasome activation were abrogated by several potassium channel inhibitors, supporting a role for potassium efflux in modulating intracellular localization of Pellino-2. The data suggest that Pellino-2 is essential for mediating the effect of potassium efflux on inflammasome activation.

中文翻译:

K+ 调节 Pellino-2 到巨噬细胞中 NLRP3 炎性体激活位点的重定位

Pellino 蛋白是参与先天免疫系统的 E3 泛素连接酶。最近,据报道 Pellino-2 可以调节小鼠 Nlrp3 炎症小体的激活。我们检查了在用 LPS 和 ATP 激活期间人 Pellino-2 在 THP1 衍生的巨噬细胞中的细胞内定位。我们观察到 Pellino-2 改变了细胞内定位,并在炎性体组装后期与炎性体蛋白 NLRP3 和 ASC 共定位。在无钾培养基中维持的细胞中也观察到与 NLRP3 和 ASC 的共定位。共定位和炎症小体激活被几种钾通道抑制剂废除,支持钾外流在调节 Pellino-2 细胞内定位中的作用。
更新日期:2021-10-12
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