Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2014; 20(27): 9106-9115
Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.9106
Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice
Hanying Zhang, Yansong Xue, Hui Wang, Yan Huang, Min Du, Qiyuan Yang, Mei-Jun Zhu
Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States
Hanying Zhang, Hui Wang, Yan Huang, Department of Animal Science, University of Wyoming, Laramie, WY 82071, United States
Min Du, Qiyuan Yang, Department of Animal Science, Washington State University, Pullman, WA 99164, United States
Author contributions: Zhang H performed research; Xue Y, Wang H, Huang Y and Yang Q contributed analytic tools; Zhang H and Zhu MJ analyzed data; Zhang H, Du M and Zhu MJ wrote the paper.
Supported by USDA-AFRI, No. 2009-65203-05716; NIH, No. 1R15HD073864; and NIH-INBRE, No. P20RR016474
Correspondence to: Dr. Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States. meijun.zhu@wsu.edu
Telephone: +1-509-3354016 Fax: +1-509-3354815
Received: December 6, 2013
Revised: January 7, 2014
Accepted: March 5, 2014
Published online: July 21, 2014
Processing time: 227 Days and 7.1 Hours
Abstract

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.

Keywords: Colitis; Interleukin-10; Inflammation; Inflammatory bowel disease; Mast cells; Mice

Core tip: Colitis is characterized by chronic inflammation and mast cells accumulate at the pathological sites, implicating their mediating roles, but the exact roles of mast cells in colitis remain poorly defined and controversial. In this study, the authors cross-bred mast cell-deficient mice with interleukin-10-deficient mice to investigate the role of mast cells in gut inflammation and the onset of colitis. Data show that mast cells have protective roles in the development of colitis by suppressing Th1 type immune response and inflammation, altering gut microbiota composition, improving gut epithelial barrier function, and reducing epithelial damage.