From model cell line to in vivo gene expression: disease-related intestinal gene expression in IBD.

H A Schulze, R Häsler, N Mah, T Lu, S Nikolaus, C M Costello, S Schreiber
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Genes and immunity
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Crohn''s disease (CD) and ulcerative colitis (UC) are subforms of inflammatory bowel diseases (IBD). Genetic and environmental factors influencing the onset and course of the diseases have been recently identified. This study uses a two-step approach to detect genes involved in the pathogenesis of IBD by microarray analysis and real-time PCR (RT-PCR). In a first step, microarray expression screening was used to obtain tumour necrosis factor-alpha (TNF-alpha) induction profiles of two human cell lines to represent the tissue cell types involved in IBD. In a second step, a subset of differentially expressed genes was examined by real-time PCR in intestinal biopsy samples of normal controls (NC) compared with UC and CD patients, as well as to a cohort of patients suffering from intestinal diseases other than IBD. Data were obtained from 88 CD, 88 UC, 53 non-IBD patients (inflammatory control), DC and 45 NC individuals. The experimental design enabled the identification of disease-specific expressed genes. DnaJ (Hsp40) homologue, subfamily B, member 5 (DNAJB5) was downregulated in intestinal biopsy samples of the UC cohort compared with NC. A difference in JUNB expression levels was observed by comparing biopsy samples from inflamed and non-inflamed areas of UC patients. Transcript expression differences between IBD and control cohorts were found by examining histamine N-methyltransferase (HNMT), interleukin-1A (IL-1A) and proplatelet basic protein (PPBP) expression. The experimental procedure represents an approach to identify disease-relevant genes, which is applicable to any disease where appropriate model systems are available.