title: Whole-genome microarray analysis and functional characterization reveal distinct gene expression profiles and patterns in two mouse models of ileal inflammation.
abstract: BACKGROUND
  Although a number of intestinal inflammatory conditions pertain to the ileum, whole-genome gene expression analyses in animal models of ileal inflammation are lacking to date. Therefore, we aimed to identify and characterize alterations in gene expression in the acutely inflamed ileum of two murine models of intestinal inflammation, namely intestinal schistosomiasis and TNBS-induced ileitis, compared to healthy controls. To this end, we used whole-genome microarrays, followed by bioinformatics analyses to detect over-represented Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology categories.
  
  
  RESULTS
  Following screening of almost all known mouse genes and transcripts represented on the array, intestinal schistosomiasis and TNBS-induced ileitis yielded 207 and 1417 differentially expressed genes, respectively, with only 30 overlapping concordantly changed genes. Functional category groups consisting of complement and coagulation cascades, extracellular matrix (ECM)-receptor interaction, Fc epsilon receptor I signaling pathways and protein activation cascade, cell adhesion categories were over-represented in the differential gene list of intestinal schistosomiasis. Antigen processing and presentation, cell adhesion molecules, ABC transporters, Toll-like receptor signaling pathways and response to chemical stimulus categories were over-represented in the differential gene list of TNBS-induced ileitis. Although cytokine-cytokine receptor interaction, intestinal immune network for IgA production, focal adhesion pathways and immune, inflammatory and defense response categories were over-represented in the differential gene lists of both inflammation models, the vast majority of the associated genes and changes were unique to each model.
  
  
  CONCLUSIONS
  This study characterized two models of ileal inflammation at a whole-genome level and outlined distinct gene expression profiles and patterns in the two models. The results indicate that intestinal schistosomiasis involves Th2 responses, complement activation, protein activation and enhanced ECM turnover, while TNBS-induced ileitis involves Th17 responses, defective antigen processing and presentation and altered Toll-like receptor-mediated responses. Signs of an impaired epithelial barrier are apparent in both inflammation models. Furthermore, the comprehensive differential gene list and functional groups provided by this study constitute an interesting starting point to explore new targets and extended functional networks dealing with small bowel inflammation.
authors.affiliation: Department of Veterinary Sciences, Laboratory of Cell Biology and Histology, University of Antwerp, Groenenborgerlaan 171, Antwerp B-2020, Belgium.
authors.forename: Leela Rani
authors.initials: LR
authors.lastname: Avula
authors.forename: Dries
authors.initials: D
authors.lastname: Knapen
authors.forename: Roeland
authors.initials: R
authors.lastname: Buckinx
authors.forename: Lucia
authors.initials: L
authors.lastname: Vergauwen
authors.forename: Dirk
authors.initials: D
authors.lastname: Adriaensen
authors.forename: Luc
authors.initials: L
authors.lastname: Van Nassauw
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D016678:Genome; D007079:Ileitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D007085:Ilium / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D017455:Receptors, IgE / Q000378:metabolism; D012550:Schistosoma mansoni; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D018528:ATP-Binding Cassette Transporters; D015815:Cell Adhesion Molecules; D017455:Receptors, IgE; D051193:Toll-Like Receptors; D014302:Trinitrobenzenesulfonic Acid