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-gamma, 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.