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Altered phenotype of dextran sulfate sodium colitis in interferon regulatory factor-1 knock-out mice
Mannick, E. E., Cote, R. L., Schurr, J. R., Krowicka, H. S., Sloop, G. D., Zapata-Velandia, A., Correa, H., Ruiz, B., Horswell, R., Lentz, J. J., Byrne, P., Gastanaduy, M. M., Hornick, C. A., & Liu, Z. (2005). Altered phenotype of dextran sulfate sodium colitis in interferon regulatory factor-1 knock-out mice. Journal of Gastroenterology and Hepatology (Australia), 20(3), 371-380. https://doi.org/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.
