Abstract
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.
Keywords: Intestinal ischemia/reperfusion injury, neutrophils, 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:
Keywords: Intestinal ischemia/reperfusion injury, neutrophils, IL-17A, Wip1.
Abstract: 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:
Du J., Shen X., Zhao Y., Hu X., Sun B., Guan W., Li S. and Zhao Y., 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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