Genome-wide Gene Expression Analysis of Mucosal Colonic Biopsies and Isolated Colonocytes Suggests a Continuous Inflammatory State in the Lamina Propria of Patients with Quiescent Ulcerative Colitis

TY - JOUR

T1 - Genome-wide Gene Expression Analysis of Mucosal Colonic Biopsies and Isolated Colonocytes Suggests a Continuous Inflammatory State in the Lamina Propria of Patients with Quiescent Ulcerative Colitis

AU - Bjerrum, Jacob Tveiten

AU - Hansen, Morten

AU - Olsen, Jørgen

AU - Nielsen, Ole Haagen

AU - Bjerrum, J.T.

AU - Hansen, M.

AU - Olsen, J.

AU - Nielsen, O.H.

PY - 2010

Y1 - 2010

N2 - Background: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state. Methods: Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n = 8), quiescent UC (n = 9), and with irritable bowel syndrome (controls, n = 10). After isolation of colonocytes and subsequent extraction of total RNA, GWGE data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P 11 software (Umetrics, Umeå, Sweden). Results: A clear separation between active UC, quiescent UC, and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC and control biopsies was governed by unique profiles containing gene expressions with significant fold changes. These primarily belonged to the family of homeostatic chemokines, revealing a plausible explanation for the abnormal regulated innate immune response seen in patients with UC. Conclusions: This study has demonstrated the presence of a continuous inflammatory state in quiescent UC, which seems to reflect an altered gene expression profile of lamina propria cells.

AB - Background: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state. Methods: Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n = 8), quiescent UC (n = 9), and with irritable bowel syndrome (controls, n = 10). After isolation of colonocytes and subsequent extraction of total RNA, GWGE data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P 11 software (Umetrics, Umeå, Sweden). Results: A clear separation between active UC, quiescent UC, and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC and control biopsies was governed by unique profiles containing gene expressions with significant fold changes. These primarily belonged to the family of homeostatic chemokines, revealing a plausible explanation for the abnormal regulated innate immune response seen in patients with UC. Conclusions: This study has demonstrated the presence of a continuous inflammatory state in quiescent UC, which seems to reflect an altered gene expression profile of lamina propria cells.

U2 - 10.1002/ibd.21142

DO - 10.1002/ibd.21142

M3 - Journal article

C2 - 19834973

SN - 1078-0998

VL - 16

SP - 999

EP - 1007

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

IS - 6

ER -