Altered phenotype of dextran sulfate sodium colitis in interferon regulatory factor-1 knock-out mice

• Published in: Journal of gastroenterology and hepatology Vol. 20; no. 3; pp. 371 - 380
• Main Authors: MANNICK, ELIZABETH E, COTE, RAE L, SCHURR, JILL R, KROWICKA, HALINA S, SLOOP, GREGORY D, ZAPATA-VELANDIA, ADRIANA, CORREA, HERNAN, RUIZ, BERNARDO, HORSWELL, RONALD, LENTZ, JENNIFER J, BYRNE, PATRICK, GASTANADUY, M MARIELLA, HORNICK, CONRAD A, LIU, ZHIYUN
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01.03.2005; Blackwell Science
• Subjects: Adenocarcinoma - etiology; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Chronic Disease; colitis; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - genetics; Colitis, Ulcerative - metabolism; Colon - drug effects; Colon - pathology; Colonic Neoplasms - etiology; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Dextran Sulfate - toxicity; Disease Models, Animal; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; dysplasia; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Interferon Regulatory Factor-1; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; microarray; Microarray Analysis; mouse; Other diseases. Semiology; Pharmacology. Drug treatments; Phenotype; Phosphoproteins - genetics; Phosphoproteins - metabolism; Polymerase Chain Reaction; Precancerous Conditions; RNA - genetics; Spectrometry, Fluorescence; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Water; RNA; Inflammatory disease; Blood substitute; Sodium sulfate; Intestinal disease; Antiviral; Suppressor; Tumor; Colon; Transcription factor; Dysplasia; Cytokine; Rodentia; Gene expression; Real time; Dextran; Polymerase chain reaction; Crohn disease; Vertebrata; Phenotype; microarray; Mammalia; Treatment; Mouse; Animal; Digestive diseases; Interferon; Models; Colitis; interferon regulatory factor-1; Molecular biology; Ulcerative colitis
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2005.03573.x

Background and Aims: Interferon regulatory factor‐1 (IRF‐1) is a transcription factor with antiviral, proinflammatory and tumor suppressor properties. We examined the role of IRF‐1 in dextran sulfate sodium colitis, a murine model of inflammatory bowel disease, to determine if absence of the gene would protect against colitis. Methods: C57BL/6J mice with a targeted disruption of IRF‐1 and wild‐type C57BL/6J controls received five 7‐day cycles of 2% dextran sulfate sodium alternating with five 7‐day cycles of water. Colonic tissue was formalin fixed for histological analysis and total RNA extracted for gene chip and SYBR green real‐time polymerase chain reaction (PCR) analysis. Results: Histological analysis revealed increased distortion of crypt architecture in the dextran sulfate sodium‐treated, IRF‐1 –/– animals as compared to dextran sulfate sodium‐treated wild‐type animals. Five of 15 dextran sulfate sodium‐treated IRF‐1 –/– mice, but only one of 14 dextran sulfate sodium‐treated wild‐type mice, developed colonic dysplasia. Microarray analysis comparing colonic gene expression in IRF‐1 –/– and wild‐type animals revealed decreased expression of caspases, genes involved in antigen presentation, and tumor suppressor genes in the IRF‐1 –/– animals. Increased expression of genes involved in carcinogenesis and immunoglobulin and complement genes was also noted in the knock‐out animals. Conclusions: Absence of IRF‐1 is not protective in dextran sulfate sodium colitis.