Wip1-deficient neutrophils significantly promote intestinal ischemia/reperfusion injury in mice

Curr Mol Med. 2015;15(1):100-8. doi: 10.2174/1566524015666150114122929.


Wip1 is a serine/threonine protein phosphatase which plays a critical role in neutrophil development and maturation. In the present study, we used a neutrophil-dependent 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental
  • Interleukin-17 / genetics
  • Intestinal Mucosa / metabolism*
  • Intestines / pathology
  • Mice
  • Mice, Knockout
  • Neutrophils / metabolism
  • Neutrophils / physiology*
  • Oxidative Stress / genetics
  • Phosphoprotein Phosphatases / deficiency
  • Phosphoprotein Phosphatases / genetics*
  • Protein Phosphatase 2C
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology
  • Tumor Necrosis Factor-alpha / genetics


  • Interleukin-17
  • Tumor Necrosis Factor-alpha
  • Phosphoprotein Phosphatases
  • Ppm1d protein, mouse
  • Protein Phosphatase 2C