title: Activation of indoleamine 2,3-dioxygenase by LPS in a porcine model.
abstract: Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for the degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway, and its increased activation is associated with immunologic disorders. Because the specific role of IDO activation is not yet completely clear, the aim of the present study was to establish a pig model of IDO activation for further research. The activation of IDO in pigs was induced experimentally by LPS stimulation in vivo and ex vivo. IDO activation was characterized by measuring Trp, Trp metabolites and IDO protein expression in blood, liver, lung, muscle and different brain areas. The results show that the in vivo LPS administration induced increased plasma concentrations of TNF-α and IL-10, a depletion of Trp and an increase of Kyn, indicating an elevated enzymatic activity of IDO. This was supported by an LPS-induced IDO protein expression in blood, liver and lung. The ex vivo LPS stimulation also resulted in increased TNF-α concentrations and an IDO activation, characterized by an increase of Trp metabolites and IDO protein expression. In conclusion, our data emphasize that the LPS stimulation is a suitable model for IDO activation in the domestic pig, which provides a basis for further research on immunoregulatory IDO functions.
authors.affiliation: 1Behavioural Physiology Research Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Wirthgen
authors.forename: Margret
authors.initials: M
authors.lastname: Tuchscherer
authors.forename: Winfried
authors.initials: W
authors.lastname: Otten
authors.forename: Grazyna
authors.initials: G
authors.lastname: Domanska
authors.forename: Karin
authors.initials: K
authors.lastname: Wollenhaupt
authors.forename: Armin
authors.initials: A
authors.lastname: Tuchscherer
authors.forename: Ellen
authors.initials: E
authors.lastname: Kanitz
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000276:immunology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D005240:Feasibility Studies; D006801:Humans; D007154:Immune System Diseases / Q000201:enzymology / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D008297:Male; D023421:Models, Animal; D013552:Swine; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007737:Kynurenine; D014364:Tryptophan
keywords: 3-dioxygenase; Indoleamine 2; LPS; kynurenine pathway; pig