Author(s)

Simon Haarder^1,2, Per W. Kania², Thomas Lindebo Holm³, Maki Ohtani², Kurt Buchmann²

¹Novo Nordisk-LIFE In Vivo Pharmacology Centre, Frederiksberg, Denmark.
²Laboratory of Aquatic Pathobiology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
³Global Research, Novo Nordisk A/S, Malov, Denmark.

Crohn’s disease and ulcerative colitis—inflammatory bowel diseases (IBD)—are chronic conditions with an inadequately understood pathogenesis. Employing a set of novel molecular markers in a gene expression assay (qPCR), we have used adult zebrafish to investigate two acute inflammatory models, induced by the haptenizing agents oxazolone and TNBS. In addition, goblet cell dynamics in the scales and intestine and 5-HT (serotonin) in intestinal tissues were investigated through optical projection tomography. Gene expression studies revealed a distinct and significant upregulation of proinflammatory cytokines, acute-phase reactants and metalloprotease 9 in both chemical models, primarily after 72 hours. In comparison, transcription factors and cytokines associated with Th1 and Th17 (Crohn’s) and Th2 (ulcerative colitis) were mainly not affected in this acute setting. However, elevated transcript levels were detected in Foxp3, IL-10 and T-bet, which are linked with tolerance and Tregs in mammals. Goblet cells in scales were depleted in both chemical models and in the intestine of oxazolone-treated fish. A marked 5-HT signal was noted in intestinal tissue of some chemically treated zebrafish. In conclusion, a distinct acute inflammatory reaction was induced in both chemical models. Further, oxazolone and TNBS did not result in clear-cut Th2 and Th1/Th17 pathway signaling at this early timepoint, but the applied molecular tools may provide further insight to the IBD pathogenesis and translational value of the IBD zebrafish model.

IBD, Zebrafish, qPCR, Disease Model, OPT

Haarder, S. , Kania, P. , Lindebo Holm, T. , Ohtani, M. and Buchmann, K. (2016) Comparison of Two Chemically-Induced Colitis-Models in Adult Zebrafish, Using Optical Projection Tomography and Novel Transcriptional Markers. Open Journal of Immunology, 6, 154-180. doi: 10.4236/oji.2016.64016.