title: Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice.
abstract: OBJECTIVE
  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 α and interferon γ in DKO mice than that in IL-10-deficient mice.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States.
authors.forename: Hanying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Du
authors.affiliation: Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Hanying Zhang, Yansong Xue, Mei-Jun Zhu, School of Food Science, Washington State University, Pullman, WA 99164, United States.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005838:Genotype; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D009195:Peroxidase; D019009:Proto-Oncogene Proteins c-kit
keywords: Colitis; Inflammation; Inflammatory bowel disease; Interleukin-10; Mast cells; Mice
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