TY - JOUR
T1 - Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice
AU - Zhang, Hanying
AU - Xue, Yansong
AU - Wang, Hui
AU - Huang, Yan
AU - Du, Min
AU - Yang, Qiyuan
AU - Zhu, Mei Jun
N1 - Publisher Copyright:
© 2014 Baishideng Publishing Group Inc. All rights reserved.
PY - 2014/7/21
Y1 - 2014/7/21
N2 - 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 (KitW-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 α and interferon γ 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.
AB - 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 (KitW-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 α and interferon γ 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.
KW - Colitis
KW - Inflammation
KW - Inflammatory bowel disease
KW - Interleukin-10
KW - Mast cells
KW - Mice
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U2 - 10.3748/wjg.v20.i27.9106
DO - 10.3748/wjg.v20.i27.9106
M3 - Article
C2 - 25083083
AN - SCOPUS:84905380032
SN - 1007-9327
SP - 9106
EP - 9115
JO - World journal of gastroenterology
JF - World journal of gastroenterology
IS - 27
ER -