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

Journal of Gastroenterology and Hepatology (Australia) - Tập 20 Số 3 - Trang 371-380 - 2005
Elizabeth E. Mannick1,2, RAE L COTE3,2, Jill R. Schurr4, HALINA S KROWICKA1, Gregory D. Sloop3, Adriana M. Zapata-Velandia1,2, Hernán Correa3, Bernardo Ruiz3, Ronald Horswell2, Jennifer J Lentz1,2, Patrick J. Byrne4, Mariella Gastañaduy1,2, Conrad A. Hornick5, Zhiyun Liu1
1Departments of Pediatrics, New Orleans, LA, USA and
2Louisiana State University, Stanley S. Scott Cancer Center,
3Departments of Pathology, New Orleans, LA, USA
4Departments of Genetics, New Orleans, LA, USA
5Departments of Physiology, New Orleans, LA, USA

Tóm tắt

AbstractBackground 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.

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Journal of Gastroenterology and Hepatology (Australia)

Tập 20 Số 3

371-380

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