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

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9106-9115
Number of pages10
JournalWorld journal of gastroenterology
Issue number27
DOIs
StatePublished - Jul 21 2014
Externally publishedYes

Keywords

  • Colitis
  • Inflammation
  • Inflammatory bowel disease
  • Interleukin-10
  • Mast cells
  • Mice

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint

Dive into the research topics of 'Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice'. Together they form a unique fingerprint.

Cite this