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Publication : Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice.

First Author  Zhang H Year  2014
Journal  World J Gastroenterol Volume  20
Issue  27 Pages  9106-15
PubMed ID  25083083 Mgi Jnum  J:328791
Mgi Id  MGI:6843652 Doi  10.3748/wjg.v20.i27.9106
Citation  Zhang H, et al. (2014) Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice. World J Gastroenterol 20(27):9106-15
abstractText  AIM: To test the role of mast cells in gut inflammation and colitis using interleukin (IL)-10-deficient mice as an experimental model. METHODS: Mast cell-deficient (Kit (W-sh/W-sh) ) mice were crossbred with IL-10-deficient mice to obtain double knockout (DKO) mice. The growth, mucosal damage and colitis status of DKO mice were compared with their IL-10-deficient littermates. RESULTS: DKO mice exhibited exacerbated colitis compared with their IL-10-deficient littermates, as shown by increased pathological score, higher myeloperoxidase content, enhanced Th1 type pro-inflammatory cytokines and inflammatory signaling, elevated oxidative stress, as well as pronounced goblet cell loss. In addition, deficiency in mast cells resulted in enhanced mucosal damage, increased gut permeability, and impaired epithelial tight junctions. Mast cell deficiency was also linked to systemic inflammation, as demonstrated by higher serum levels of tumor necrosis factor alpha and interferon gamma in DKO mice than that in IL-10-deficient mice. CONCLUSION: Mast cell deficiency in IL-10-deficient mice resulted in systematic and gut inflammation, impaired gut barrier function, and severer Th1-mediated colitis when compared to mice with only IL-10-deficiency. Inflammation and impaired gut epithelial barrier function likely form a vicious cycle to worsen colitis in the DKO mice.
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