Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease.
BACKGROUND
Mouse models of inflammatory bowel diseases (IBD) are used to unravel the pathophysiology of IBD and to study new treatment modalities, but their relationship to Crohn's disease (CD) or ulcerative colitis (UC) is speculative.


METHODS
Using Agilent mouse TOX oligonucleotide microarrays, we analyzed colonic gene expression profiles in three widely used models of experimental colitis. In 2 of the models (TNBS and DSS-induced colitis), exogenous agents induce the colitis. In the third model the colitis is induced after transfer of a T-cell population (CD4(+)CD45RB(high) T cells) that lacks regulatory cells into an immunodeficient host.


RESULTS
Compared with control mice, in DSS, TNBS, and the CD45RB transfer colitis mice, 387, 21, and 582 genes were more than 2-fold upregulated in the intestinal mucosa. Analyses of exclusively shared gene expression profiles between the different models revealed that DSS/transfer colitis share 69 concordantly upregulated genes, DSS/TNBS 6, and TNBS/transfer colitis 1. Seven genes were upregulated in all three models. The CD45RB transfer model expression profile included the most genes that are known to be upregulated in IBD. Of 32 genes that are known to change transcriptional activity in IBD (TNF, IFN-gamma, Ltbeta, IL-6, IL-16, IL-18R1, IL-22, CCR2, 7, CCL2, 3, 4, 5, 7, 11, 17, 20, CXCR3, CXCL1, 5, 10, Mmp3, 7,9, 14, Timp1, Reg3gamma, and Pap, S-100a8, S-100a9, Abcb1, and Ptgs2), 2/32 are upregulated in TNBS, 15/32 are upregulated or downregulated in DSS and 30/32 are upregulated or downregulated in the CD45RB transfer colitis.


CONCLUSIONS
The pattern of gene expression in the CD45RB transfer model most closely reflects altered gene expression in IBD.
te Velde
Anje A
AA
Center of Experimental and Molecular Medicine, AMC, Amsterdam, The Netherlands. a.a.tevelde@amc.uva.nl
de Kort
Floor
F
Sterrenburg
Ellen
E
Pronk
Inge
I
ten Kate
Fiebo J W
FJ
Hommes
Daniel W
DW
van Deventer
Sander J H
SJ
D000818:Animals; D003092:Colitis / Q000139:chemically induced; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014302:Trinitrobenzenesulfonic Acid
D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D017493:Leukocyte Common Antigens