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

Autor: Mannick EE; Louisiana State University, Stanley S. Scott Cancer Center, LA, USA. elizabeth@surgery.tulane.edu, Cote RL, Schurr JR, Krowicka HS, Sloop GD, Zapata-Velandia A, Correa H, Ruiz B, Horswell R, Lentz JJ, Byrne P, Gastanaduy MM, Hornick CA, Liu Z
Jazyk: angličtina
Zdroj: Journal of gastroenterology and hepatology [J Gastroenterol Hepatol] 2005 Mar; Vol. 20 (3), pp. 371-80.
DOI: 10.1111/j.1440-1746.2005.03573.x
Abstrakt: 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.
Databáze: MEDLINE
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