title: Severity of DSS-induced colitis is reduced in Ido1-deficient mice with down-regulation of TLR-MyD88-NF-kB transcriptional networks.
abstract: Indoleamine 2,3 -dioxygenase 1 (IDO1) catalyzes L-tryptophan to kynurenine in the first and rate-limiting step of tryptophan metabolism. IDO1 is expressed widely throughout the body, with especially high expression in colonic intestinal tissues. To examine the role of IDO1 in the colon, transcriptome analysis was performed in both Ido1(-/-) and Ido1(+/+) mice. Gene set enrichment analysis identified the Inflammatory Response as the most significant category modulated by the absence of IDO1. This observation prompted us to further investigate the function of IDO1 in the development of tissue inflammation. By using DSS-induced experimental colitis mice models, we found that the disease in Ido1(-/-) mice was less severe than in Ido1(+/+) mice. Pharmacological inhibition of IDO1 by L-1MT attenuated the severity of DSS-colitis as well. Transcriptome analyses revealed that pathways involving TLR and NF-kB signaling were significantly down-regulated by the absence of IDO1. Furthermore, dramatic changes in TLR and NF-kB signaling resulted in substantial changes in the expression of many inflammatory cytokines and chemokines. Numbers of inflammatory cells in colon and peripheral blood were reduced in IDO1 deficiency. These findings suggest that IDO1 plays important roles in producing inflammatory responses and modulating transcriptional networks during the development of colitis.
authors.affiliation: Department of Food and Nutrition, Seoul National University, Seoul 151-742, Korea.
authors.forename: Woo-Jeong
authors.initials: WJ
authors.lastname: Shon
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Young-Kwan
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Seoul National University, Seoul 151-742, Korea.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Department of Food and Nutrition, Seoul National University, Seoul 151-742, Korea.|Research institution of human ecology, Seoul National University, Seoul 151-742, Korea.
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000187:drug effects; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D012967:Sodium Dodecyl Sulfate; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; C583637:IDO1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D012967:Sodium Dodecyl Sulfate; C028129:tryptophan methyl ester; D014364:Tryptophan