Department of Dermatology, West China Hospital, West China School of Medicine, Sichuan University, Chengdu 610041, China; Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Exp Cell Res. 2018 Jul 15;368(2):167-173. doi: 10.1016/j.yexcr.2018.04.023. Epub 2018 Apr 24.
ER-localized proteins have been reported function in endoplasmic reticulum, unfolded protein degradation and destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system, but their function in the chemotaxis of macrophage cells remained un-addressed. Here, we showed that ER protein with ubiquitin like domain 1(Herpud1) was upregulated in IL-4-treated M2 macrophage cells and its expression pattern was similar with macrophage polarization markers, such as Arg1, Mrc1 and Fizz1. Inhibition of Herpud1 by using specific target shRNA decreased these marker's expression at mRNA and protein level in IL-4-treated or -untreated M2 macrophage cells. IL-4 treatment promoted M2 macrophage cell migration and polarization, but this promotion was weakened by Herpud1 depletion and we got similar results by inhibition of ER stress response with chemical molecule 4-phenylbutyric acid (4-PBA) in IL-4-treated or untreated-M2 macrophage cells with Herpud1 overexpression. These results indicated that depending on ER-associated protein degradation (ERAD) to help unfolded protein degradation or destruction is not the only function of Herpud1 and acting as a mediator of IL-4 induced macrophage activation and polarization maybe another unrevealed function, elucidating the role of Herpud1-associated M2 macrophage cell polarization and activation are helpful for exploration the function of macrophage cells in immune response.
内质网定位蛋白已被报道在内质网中发挥作用，在未折叠蛋白降解和错误折叠蛋白的破坏中发挥作用，通过内质网相关蛋白降解（ERAD）系统，但它们在巨噬细胞趋化中的作用仍未得到解决。在这里，我们表明，白细胞介素-4（IL-4）处理的 M2 巨噬细胞中上调了具有泛素样结构域 1（Herpud1）的内质网蛋白，其表达模式与巨噬细胞极化标志物相似，如 Arg1、Mrc1 和 Fizz1。使用特异性靶 shRNA 抑制 Herpud1，可降低 IL-4 处理或未处理的 M2 巨噬细胞中这些标志物的 mRNA 和蛋白水平。白细胞介素-4（IL-4）处理促进 M2 巨噬细胞迁移和极化，但 Herpud1 耗竭削弱了这种促进作用，我们在 IL-4 处理或未处理的 M2 巨噬细胞中用化学分子 4-苯丁酸（4-PBA）抑制内质网应激反应并过表达 Herpud1 时，也得到了类似的结果。这些结果表明，依赖内质网相关蛋白降解（ERAD）来帮助未折叠蛋白降解或破坏不是 Herpud1 的唯一功能，作为白细胞介素-4 诱导的巨噬细胞激活和极化的介质可能是另一个未被揭示的功能，阐明 Herpud1 相关 M2 巨噬细胞极化和激活的作用有助于探索巨噬细胞在免疫反应中的功能。
