Qingqing Liu1, Noam Harpaz1. 1. The Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: Collagenous colitis [CC] is a common idiopathic cause of chronic watery diarrhoea. We investigated its pathogenesis by means of gene expression analysis. METHODS: We analysed the expression of genes implicated in immunological and inflammatory pathways in paired colonic biopsies of histologically involved and uninvolved mucosa from five patients with histologically patchy CC, in pooled colonic biopsies of eight other patients with diffuse CC, and in pooled biopsies of eight normal controls. Analyses were performed with the Nanostring nCounter system. Expression ratios were generated and confirmed by quantitative reverse transcription PCR. RESULTS: CC mucosa was characterized by enhanced expression of nitric oxide synthase 2; of matrix metalloproteinases 3 and 9 and tissue inhibitor of metalloproteinase 1, but not transforming growth factor β1; of mediators of T-helper 1 immunity including interleukins 12A [IL12A], 12B, IL12 receptor B1 and interferon γ; of immune mediators of the leukocyte immunoglobulin-like receptor subfamily B; and of multiple T cell cytokines and their receptors. The mitogen-activated protein kinase signalling pathway was unchanged. There were no increases in IL22, IL22RA2 or tumour necrosis factor α, which are reportedly elevated in chronic inflammatory bowel disease. In four of five patients with patchy CC, similar gene expression profiles were observed in histologically involved and uninvolved mucosa. CONCLUSIONS: CC is characterized by altered expression of a limited repertoire of genes involved in nitric oxide synthesis, extracellular matrix remodelling, T-helper 1 immunity and immune modulation. The abnormal gene expression in patchy CC may be expressed in mucosa with and without histological disease manifestations.
BACKGROUND:Collagenous colitis [CC] is a common idiopathic cause of chronic watery diarrhoea. We investigated its pathogenesis by means of gene expression analysis. METHODS: We analysed the expression of genes implicated in immunological and inflammatory pathways in paired colonic biopsies of histologically involved and uninvolved mucosa from five patients with histologically patchy CC, in pooled colonic biopsies of eight other patients with diffuse CC, and in pooled biopsies of eight normal controls. Analyses were performed with the Nanostring nCounter system. Expression ratios were generated and confirmed by quantitative reverse transcription PCR. RESULTS: CC mucosa was characterized by enhanced expression of nitric oxide synthase 2; of matrix metalloproteinases 3 and 9 and tissue inhibitor of metalloproteinase 1, but not transforming growth factor β1; of mediators of T-helper 1 immunity including interleukins 12A [IL12A], 12B, IL12 receptor B1 and interferon γ; of immune mediators of the leukocyte immunoglobulin-like receptor subfamily B; and of multiple T cell cytokines and their receptors. The mitogen-activated protein kinase signalling pathway was unchanged. There were no increases in IL22, IL22RA2 or tumour necrosis factor α, which are reportedly elevated in chronic inflammatory bowel disease. In four of five patients with patchy CC, similar gene expression profiles were observed in histologically involved and uninvolved mucosa. CONCLUSIONS: CC is characterized by altered expression of a limited repertoire of genes involved in nitric oxide synthesis, extracellular matrix remodelling, T-helper 1 immunity and immune modulation. The abnormal gene expression in patchy CC may be expressed in mucosa with and without histological disease manifestations.
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