Gene expression patterns in experimental colitis in IL-10-deficient mice

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Abstract

Background:

While others have described gene expression patterns in humans with inflammatory bowel diseases and animals with chemically induced colitis, a genome-wide comparison of gene expression in genetically susceptible animals that develop spontaneous colitis has not been reported.

Methods:

We used microarray technology to compare gene expression profiles in cecal specimens from specific pathogen-free IL10-deficient (IL10−/−) mice with colitis and normal wildtype (WT) mice. RNA isolated from ceca of IL10−/− and WT mice was subjected to microarray analysis. The results were confirmed by real-time polymerase chain reaction (PCR) and immunofluorescence microscopy of selected molecules. Expression of the selected genes in dextran sodium sulfate (DSS)-treated mice with colitis and epithelial cell lines activated with pathophysiologic stimuli was measured by real-time PCR.

Results:

Histological inflammation of the colon and IL-12/23p40 secretion from intestinal explants were greater in IL10−/− and DSS-treated mice versus WT and untreated mice. Microarray analysis demonstrated >10-fold induction of the following molecules in the ceca of IL10−/− mice: mitochondrial ribosomal protein-L33, aquaporin-4, indoleamine-pyrrole-2,3-dioxygenase, and MHC class II with 63, 25, 20, and 12-fold increases, respectively. Cytochrome-P450, pancreatic lipase-related protein-2, and transthyretin were downregulated in IL10−/− mice. MHC II was increased throughout the colon, and aquaporin-4 was increased in the basolateral aspect of cecal epithelial cells. MHC II mRNA was increased in epithelial cells treated with IFN-γ, but not TNF or Toll-like receptor ligands.

Conclusions:

Although most upregulated genes in experimental colitis are immune-related, aquaporin-4 and mitochondrial ribosomal protein-L33, which have not been previously associated with inflammation, were most highly upregulated.

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