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J Gastroenterol Hepatol ; 20(3): 371-80, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15740479

RESUMEN

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.


Asunto(s)
Colitis Ulcerosa/genética , Proteínas de Unión al ADN/genética , Sulfato de Dextran/toxicidad , Fosfoproteínas/genética , ARN/genética , Adenocarcinoma/etiología , Adenocarcinoma/genética , Adenocarcinoma/patología , Animales , Enfermedad Crónica , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Colon/efectos de los fármacos , Colon/patología , Neoplasias del Colon/etiología , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Estudios de Seguimiento , Expresión Génica , Factor 1 Regulador del Interferón , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Análisis por Micromatrices , Fenotipo , Fosfoproteínas/metabolismo , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas , Espectrometría de Fluorescencia
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