Altered phenotype of dextran sulfate sodium colitis in interferon regulatory factor-1 knock-out mice.
OBJECTIVE
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.
Mannick
Elizabeth E
EE
Louisiana State University, Stanley S. Scott Cancer Center, LA, USA. elizabeth@surgery.tulane.edu
Cote
Rae L
RL
Schurr
Jill R
JR
Krowicka
Halina S
HS
Sloop
Gregory D
GD
Zapata-Velandia
Adriana
A
Correa
Hernan
H
Ruiz
Bernardo
B
Horswell
Ronald
R
Lentz
Jennifer J
JJ
Byrne
Patrick
P
Gastanaduy
M Mariella
MM
Hornick
Conrad A
CA
Liu
Zhiyun
Z
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000818:Animals; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D015870:Gene Expression; D050856:Interferon Regulatory Factor-1; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions; D012313:RNA / Q000235:genetics*; D013050:Spectrometry, Fluorescence
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012313:RNA; D016264:Dextran Sulfate