Wip 1 inhibits intestinal inflammation in inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronically intestinal autoimmune disease, the pathological mechanisms of which are not very clear. Wild type p-53 induced phosphatase 1 (Wip1), a serine/threonine protein phosphatase, has been reported to negatively regulate the inflammation in sepsis. However, the role of Wip1 in IBD is not very clear. Therefore, colonic tissues and peripheral blood from patients with IBD and healthy controls were collected to analyzed mRNA and protein expression of Wip1 using the method of qPCR and immunohistochemistry. Immune cells of neutrophils, CD4⁺ T cells, CD8⁺ T cells, B cells, monocytes and intestinal epithelial cells were isolated to analyze Wip1 expression by means of qPCR. Expression of Wip 1 was analyzed after the cells were stimulated by various of cytokines. DSS-colitis model was induced on the wild type (WT) and Wip 1 knock out (Wip1^-/-) mice, and cytokines expression were analyzed in intestinal lamina propria from WT and Wip1^-/- mice. Neutrophil specific markers were examined in intestinal lamina propria from WT and Wip1^-/- mice. Moreover, neutrophils were isolated from bone marrow of WT and Wip1^-/- mice to examine neutrophil migration with or without inhibitors of signaling pathway in vitro. The expression of Wip 1 mRNA and protein were found to be significantly decreased in patients with active IBD compared with healthy controls. And Wip 1 was mainly expressed on neutrophils from peripheral blood and colonic tissues. Moreover, expression of Wip1 was significantly decreased on neutrophils after the stimulation of TNF-α and IFN-γ. Wip1^-/- mice were more susceptible to DSS induced colitis compared to WT mice, and expressed more pro-inflammatory cytokines (e.g. TNF-α, IFN-γ, IL-17A, etc). Moreover, expression of neutrophil specific markers (e.g. Ly6G, CD11b, elastase, etc) was also increased in Wip1^-/- mice. The migration of neutrophils from the bone marrow of Wip1 mice was marked increased, which was mediated by MAPK-P38 signaling pathway. Wip1 plays an importantly protective role in the pathogenesis of IBD. Therefore, Wip1 may be used a new targets in the treatment for IBD in the future.