Inflammatory bowel disease (IBD) is a progressive, recurrent gastrointestinal disorder influenced by genetic, immunoregulatory and environmental factors and often requiring surgery for treatment. Ulcerative colitis (UC) and Crohn disease (CD), the two most common forms of IBD, have similar demographic and epidemiological features, but differ in intestinal tissue damage and prognosis. UC is associated with mucosal and submucosal injury involving the rectum and adjacent colon, whereas CD is associated with extensive transmural damage involving any segment of the colon. Both phenotypes are likely the outcome of small changes in expression of many regulatory genes, with consequent changes in expression of genes encoding cellular and extracellular matrix proteins. To understand the overall gene expression and dynamics in UC and CD we have performed expression profiling using oligonucleotide microarrays.

Resected bowel tissue from fresh UC, CD and control (cancer) surgical specimens were used to prepare total RNA. Poly(A)+ RNA was extracted from pooled total RNA to prepare biotinylated cRNA for hybridization to the Affymetrix HuGene Fl set according to the manufacturer's recommendations. After hybridization, GeneChips were washed in the Fluidics station 400 and scanned in a Hewlett-Packard GeneArray Scanner. Scanned images were analysed using the GeneChip3.1 Analysis Suite.

Probing of the UC target RNA identified fivefold or higher expression of 8 transcripts from HuGeneFLsubA array, 4 from sub B array, 8 from sub C and 29 from sub D array compared with control RNA. Two independent probings showed remarkable reproducibility (33 of 49 overexpressed transcripts in common) between experiments. Furthermore, overexpressed genes included several ‘IBD-related’ genes, such as genes encoding proteins that bind HLA class II cis-acting elements, metalloproteinases and collagen types I and IV chains. Additionally, we identified several novel genes as overexpressed or repressed in UC. Hybridization of the CD sample to sub B, C and D arrays indicate overexpression of ten transcripts at fivefold and higher levels. Compared with UC, fewer genes are overexpressed in CD; for example, in the sub D array compared with 29 overexpressed transcripts in UC, only 6 were elevated in CD, of which only 2 were unique to CD. In general, certain immunoregulatory genes, antimicrobial factor encoding genes, extracellular matrix (ECM) modulatory genes and ECM genes show altered expression in UC and CD. These studies will lead to a fundamental understanding of IBD pathogenicity, differences underlying UC and CD, and ultimately to better therapeutic approaches.