کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5530718 | 1549389 | 2016 | 8 صفحه PDF | دانلود رایگان |
- Expression of Wip1 was markedly decreased in patients with active IBD.
- Wip1 was mainly expressed on neutrophils and the expression was regulated by TNF-α.
- Knock out of Wip1 in mouse aggravated colonic inflammation.
- Neutrophils migration was increased after knock out of Wip1.
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 (Wip1â/â) mice, and cytokines expression were analyzed in intestinal lamina propria from WT and Wip1â/â mice. Neutrophil specific markers were examined in intestinal lamina propria from WT and Wip1â/â mice. Moreover, neutrophils were isolated from bone marrow of WT and Wip1â/â 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. Wip1â/â 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 Wip1â/â 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.
Journal: Cellular Immunology - Volume 310, December 2016, Pages 63-70