Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: Mucin 2-interleukin 10-deficient mice

Maria Van Der Sluis, Janneke Bouma, Audrey Vincent, Anna Velcich, Kermit L. Carraway, Hans A. Büller, Alexandra W.C. Einerhand, Johannes B. Van Goudoever, Isabelle Van Seuningen, Ingrid B. Renes

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Expression of the mucin MUC2, the structural component of the colonic mucus layer, is lowered in ulcerative colitis. Furthermore, interleukin (IL)-10 knockout (IL-10-/-) mice develop colitis and have reduced Muc2 levels. Our aim was to obtain insight into the role of Muc2 and IL-10 in epithelial protection. Muc2-IL-10 double-knockout (Muc2/IL-10DKO) mice were characterized and compared to Muc2 knockout (Muc2-/-), IL-10-/- and wild-type (WT) mice. Clinical symptoms, intestinal morphology and differences in epithelial-specific protein levels were analyzed. In addition, levels of the pro-inflammatory cytokines in colonic tissue and serum were determined. IL-10-/- mice were indistinguishable from WT mice throughout this experiment and showed no clinical or histological signs of colitis. Muc2/IL-10DKO and Muc2-/- mice showed significant growth retardation and clinical signs of colitis at 4 and 5 weeks, respectively. Muc2/IL-10DKO mice had a high mortality rate (50% survival/5 weeks) compared to the other types of mice (100% survival). Microscopic analysis of the colon of Muc2/IL-10DKO mice showed mucosal thickening, increased proliferation, superficial erosions and a diminished Muc4 expression. Furthermore, pro-inflammatory cytokines were significantly upregulated, both in tissue (mRNA) and systemically in Muc2/IL-10DKO mice. In conclusion, Muc2/IL-10DKO mice develop colitis, which is more severe in every aspect compared to Muc2 -/- and IL-10-/- mice. These data indicate that (i) in case of Muc2 deficiency, the anti-inflammatory cytokine IL-10 can control epithelial damage, though to a limited extent and (ii) the mucus layer is most likely a key factor determining colitis.

Original languageEnglish (US)
Pages (from-to)634-642
Number of pages9
JournalLaboratory Investigation
Volume88
Issue number6
DOIs
StatePublished - Jun 24 2008
Externally publishedYes

Keywords

  • Experimental colitis
  • Goblet cell
  • Inflammatory bowel diseases
  • Intestine
  • Mice
  • Mucin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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