Background: We explored the gene expression in colonic biopsies of active and inactive inflammatory bowel disease (IBD) in an extensive material of ulcerative colitis (UC) and Crohn’s disease (CD). The chemokine CXCL10 and its receptor CXCR3 were among the upregulated genes. This study examined the expression of CXCL10 and the mechanisms for its release in patients with UC or CD and in intestinal epithelial cell (IEC) lines.
Methods: A microarray gene expression analysis was done on colonic biopsies (n = 133) from patients with IBD. Biopsies were studied with immunohistochemistry for CXCL10 and CXCR3 expression. Mechanisms for CXCL10 release in peripheral blood mononuclear cells (PBMCs) and in the colonic epithelial cell lines HT-29 and SW620 were studied upon pattern recognition receptor (PRR) stimulation.
Results: CXCL10 and CXCR3 mRNA abundances were increased in biopsies from active UC and CD compared to inactive disease and controls. CXCL10 was mainly localized to mucosal epithelial cells, with increased immunostaining in active IBD. CXCR3-positive cells were scattered in the lamina propria. CXCL10 was secreted from the colonic epithelial cell lines in response to the Toll-like receptor 3 (TLR3) ligand polyinosinic: polycytidylic acid (poly(I:C)). This ligand also induced a marked release of CXCL10 in PBMCs from IBD patients and controls.
Conclusions: We identified CXCL10 and CXCR3 as upregulated genes in colonic mucosa in active IBD. The TLR3-ligand poly(I:C) markedly increased release of CXCL10 in colonic epithelial cell lines, suggesting a TLR3-mediated CXCL10 release from mucosal epithelial cells in IBD patients.
Article first published online 8 June 2012
*Department of Gastroenterology and Hepatology, St. Olav’s University Hospital, Trondheim, Norway
†Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
‡Department of Pathology and Medical Genetics, St. Olav’s University Hospital, Trondheim, Norway
§Department of Laboratory Medicine, Children’s and Women’s Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
‖Department of Infectious Diseases, St. Olav’s University Hospital, Trondheim, Norway.
Reprints: Arne K. Sandvik, MD, PhD, Department of Cancer Research and Molecular Medicine, Faculty of Medicine NTNU, P.O. Box 8905, N-7491 Trondheim, Norway (e-mail: email@example.com).
The first two authors contributed equally to this work
Supported by grants from the Liaison Committee between the Central Norway Regional Health Authority (AEØ), The Norwegian Cancer Society (to N.J.N. and M.B.) and NTNU (to Av.B.G.). This work also received funding from a research grant from the Liaison Committee between St. Olav's University Hospital and the Faculty of Medicine, NTNU. The microarray analysis was supported by the Functional Genomics Programme (FUGE) of the Norwegian Research Council.
Received April 26, 2012
Accepted May 14, 2012