Gene expression patterns in experimental colitis in IL-10-deficient mice.
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.
Hansen
Jonathan J
JJ
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Holt
Lisa
L
Sartor
R Balfour
RB
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics; D002432:Cecum / Q000276:immunology; D003092:Colitis / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D012269:Ribosomal Proteins / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D000949:Histocompatibility Antigens Class II; D012269:Ribosomal Proteins; D016753:Interleukin-10