title: Temporal colonic gene expression profiling in the recurrent colitis model identifies early and chronic inflammatory processes.
abstract: The recurrent TNBS-colitis model in BALB/c mice has been proposed as a model of Inflammatory Bowel Disease with a shifting pattern of local cytokines with the expression of Th1 cytokines during the early phase, Th17 cytokines during the intermediate phase and Th2 cytokines during late fibrotic stages. In this study, we evaluated the development of pathology in time-in conjunction with genome-wide gene expression in the colons-in response to three weekly intrarectal instillations of TNBS. During this time-frame mice develop colitis with extensive cellular infiltration of (sub)mucosa and mildly to moderately affected crypt architecture. These pathological processes were sensitive to local treatment with budesonide. Gene expression profiling confirmed an acute phase response after each intrarectal TNBS-challenge. In addition, a chronic inflammatory process developed over time particularly evident from a gradual increase in expression of mast cell related genes. The changes in pathological hallmarks were consistent with a temporal expression of mRNA encoding a selection of chemokines. In conclusion, the early stages of the recurrent TNBS-colitis model reflect several aspects of inflammatory bowel disease which are sensitive to immunomodulation.
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands. bas.kremer@tno.nl
authors.forename: Bas
authors.initials: B
authors.lastname: Kremer
authors.forename: Rob
authors.initials: R
authors.lastname: Mariman
authors.forename: Marjan
authors.initials: M
authors.lastname: van Erk
authors.forename: Tonny
authors.initials: T
authors.lastname: Lagerweij
authors.forename: Lex
authors.initials: L
authors.lastname: Nagelkerken
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D056747:Immunomodulation; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D058408:Th1-Th2 Balance; D013997:Time Factors; D059467:Transcriptome / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019819:Budesonide; D014302:Trinitrobenzenesulfonic Acid