TITLE:
Comparison of Two Chemically-Induced Colitis-Models in Adult Zebrafish, Using Optical Projection Tomography and Novel Transcriptional Markers
AUTHORS:
Simon Haarder, Per W. Kania, Thomas Lindebo Holm, Maki Ohtani, Kurt Buchmann
KEYWORDS:
IBD, Zebrafish, qPCR, Disease Model, OPT
JOURNAL NAME:
Open Journal of Immunology,
Vol.6 No.4,
December
28,
2016
ABSTRACT: 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.