TY - JOUR

T1 - Comparison of two chemically-induced colitis-models in adult zebrafish, using optical projection tomography and novel transcriptional markers

AU - Haarder, Simon

AU - Kania, Per Walter

AU - Holm, Thomas

AU - Otani, Maki

AU - Buchmann, Kurt

PY - 2016/12/20

Y1 - 2016/12/20

N2 - Crohn’s disease and ulcerative colitis—inflammatory bowel diseases (IBD)—arechronic 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 intestinaltissue of some chemically treated zebrafish. In conclusion, a distinct acute inflammatoryreaction was induced in both chemical models. Further, oxazolone andTNBS did not result in clear-cut Th2 and Th1/Th17 pathway signaling at this earlytimepoint, but the applied molecular tools may provide further insight to the IBDpathogenesis and translational value of the IBD zebrafish model.

AB - Crohn’s disease and ulcerative colitis—inflammatory bowel diseases (IBD)—arechronic 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 intestinaltissue of some chemically treated zebrafish. In conclusion, a distinct acute inflammatoryreaction was induced in both chemical models. Further, oxazolone andTNBS did not result in clear-cut Th2 and Th1/Th17 pathway signaling at this earlytimepoint, but the applied molecular tools may provide further insight to the IBDpathogenesis and translational value of the IBD zebrafish model.

U2 - 10.4236/oji.2016.64016

DO - 10.4236/oji.2016.64016

M3 - Journal article

VL - 6

SP - 154

EP - 180

JO - Open Journal of Immunology

JF - Open Journal of Immunology

SN - 2162-450X

ER -