摘要
Wip1是一种丝氨酸/苏氨酸蛋白磷酸酶,在嗜中性粒细胞的发育和成熟起着关键作用。在本研究中,我们使用了使用肠缺血/再灌注(I/R)损伤的中性粒细胞相关模型以确定氧化应激和炎症的情况下Wip1在嗜中性粒细胞功能中的作用。Wip1缺陷小鼠表现出更严重的I/R损伤,伴随嗜中性粒细胞浸润增多,趋化因子例如CXCL-1、 CXCL-2 和CCL-2和炎症细胞因子例如TNF-α和IL-17的高表达。在Wip1KOa→WT全造血嵌合体小鼠上的研究表明固有调节肠I/R损伤后的免疫细胞功能。通过从WT小鼠或IL-17, IL-17/Wip1或Wip1缺陷的小鼠过继转移中性粒细胞,我们发现 Wip1KO中性粒细胞产生更多的IL-17,最终导致更严重的肠I/R损伤。我们的发现定义Wip1为肠I/R损伤过程中性粒细胞炎症的固有调节剂。
关键词: 肠缺血/再灌注损伤,中性粒细胞,IL-17A,Wip1。
Current Molecular Medicine
Title:Wip1-Deficient Neutrophils Significantly Promote Intestinal Ischemia/Reperfusion Injury in Mice
Volume: 15 Issue: 1
Author(s): J. Du, X. Shen, Y. Zhao, X. Hu, B. Sun, W. Guan, S. Li and Y. Zhao
Affiliation:
关键词: 肠缺血/再灌注损伤,中性粒细胞,IL-17A,Wip1。
摘要: Wip1 is a serine/threonine protein phosphatase which plays a critical role in neutrophil development and maturation. In the present study, we used a neutrophildependent model of intestinal ischemia/reperfusion (I/R) injury to identify the role of Wip1 in neutrophil function under the condition of oxidative stress and inflammation. Wip1- deficient mice displayed more severe intestinal I/R injury with increased infiltration of neutrophils and higher expression of chemokines like CXCL-1, CXCL-2 and CCL-2, as well as inflammatory cytokine like TNF-α and IL-17. Studies in Wip1KOa→WT full hematopoietic chimera mice showed that Wip1 intrinsically regulated the function of immune cells after intestinal I/R injury. Through adoptive transfer of neutrophils from WT mice or mice with deficiency of IL-17, IL-17/Wip1 or Wip1, we demonstrated that Wip1KO neutrophils produced more IL-17 and eventually led to more severe intestinal I/R injury. Thus, our findings identify Wip1 as an intrinsic negative regulator of neutrophil inflammation in intestinal I/R injury process.
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Cite this article as:
J. Du, X. Shen, Y. Zhao, X. Hu, B. Sun, W. Guan, S. Li and Y. Zhao , Wip1-Deficient Neutrophils Significantly Promote Intestinal Ischemia/Reperfusion Injury in Mice, Current Molecular Medicine 2015; 15 (1) . https://dx.doi.org/10.2174/1566524015666150114122929
DOI https://dx.doi.org/10.2174/1566524015666150114122929 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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