| First Author | Sun B | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 3 | Pages | 1184-95 |
| PubMed ID | 24395919 | Mgi Jnum | J:207418 |
| Mgi Id | MGI:5556349 | Doi | 10.4049/jimmunol.1300656 |
| Citation | Sun B, et al. (2014) Phosphatase Wip1 negatively regulates neutrophil migration and inflammation. J Immunol 192(3):1184-95 |
| abstractText | Neutrophils are critically involved in host defense and tissue damage. Intrinsic signal mechanisms controlling neutrophil activities are poorly defined. We found that the expression of wild-type p53-induced phosphatase 1 (Wip1) in mouse and human neutrophils was downregulated quickly after neutrophil activation through JNK-microRNA-16 pathway. Importantly, the Wip1 expression level was negatively correlated with inflammatory cytokine productions of neutrophils in sepsis patients. Wip1-deficient mice displayed increased bactericidal activities to Staphylococcus aureus and were hypersensitive to LPS-induced acute lung damage with increased neutrophil infiltration and inflammation. Mechanism studies showed that the enhanced inflammatory activity of neutrophils caused by Wip1 deficiency was mediated by p38 MAPK-STAT1 and NF-kappaB pathways. The increased migration ability of Wip1KO neutrophils was mediated by the decreased CXCR2 internalization and desensitization, which was directly regulated by p38 MAPK activity. Thus, our findings identify a previously unrecognized function of Wip1 as an intrinsic negative regulator for neutrophil proinflammatory cytokine production and migration through multiple signal pathways. |
