Transcriptome Analysis of Ido1 Knock-out Mice with Dextran Sulfate Sodium-induced Colitis

Abstract

Tryptophan involves in a range of biological processes including protein and biogenic nitrogen-compounds synthesis. It is metabolized to kynurenine by indoleamine 2,3-dioxygenase 1 (IDO1) that is the first rate limiting enzyme. IDO1 expresses ubiquitously in the body with heightened expressions in intestinal tissues. To examine the function of IDO1 in colon, transcriptome analysis using microarray was performed in both Ido1 knock-out (Ido1-/-) mice and wild type (Ido1+/+) mice. Differentially expressed genes in comparison of Ido1-/- and Ido1+/+ mice were categorized based upon their biological functions. Gene set enrichment analysis showed that inflammatory response was the most significant category which was modulated by IDO1 gene. This observation prompted us to study the function of IDO1 in inflammatory bowel disease mouse model. In DSS-induced ulcerative colitis model, the disease was more severely developed in Ido1+/+ mice compared with Ido1-/- mice. Total RNAs of inflamed colon tissues from both Ido1+/+ and Ido1-/- mice were applied to microarray in order to find the significant signaling pathways affected by Ido1 deficiency. TLR signaling and NF-kB signaling were turned out to be responsible for generating the difference in disease progression between those two genotypes. Dramatic changes in TLR signaling and NF-kB signaling resulted in substantial changes in expressions of many pro- and anti- inflammatory cytokines and chemokines. These findings suggest that IDO1 play roles in producing inflammatory responses and modulating transcriptional networks during colitis development.