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dc.contributor.authorYadav, M.C.
dc.contributor.authorBurudi, E.M.E.
dc.contributor.authorAlirezaei, M.
dc.contributor.authorFlynn, C.C.
dc.contributor.authorWatry, D.D.
dc.contributor.authorLanigan, C.M.
dc.contributor.authorFox, H.S.
dc.identifier.citationYadav, M.C.; Burudi, E.M.; Alirezaei, M.; Flynn, C.C.; Watry, D.D.; Lanigan, C.M., Fox, H.S. 2007. IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4. Glia 55(13):1385-1396.en_US
dc.description.abstractIndoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, has been implicated in the pathogenesis of various neurological disorders. IDO expression is induced by IFN-gamma and leads to neurotoxicity by generating quinolinic acid. Additionally, it inhibits the immune response through both tryptophan depletion and generating other tryptophan catabolites. IL-4 and IL-13 have been shown to control IDO expression by antagonizing the effects of IFN-gamma in different cell types. Here, we investigated the effects of these cytokines on IDO expression in microglia. Interestingly, we observed that both IL-4 and IL-13 greatly enhanced IFN-gamma-induced IDO expression. However, tryptophanyl-tRNA synthetase (WRS), which is coinduced with IDO by IFN-gamma, is downregulated by IL-4 and IL-13. The effect of IL-4 and IL-13 was independent of STAT-6. Modulation of IDO but not WRS was eliminated by inhibition of protein phosphatase 2A (PP2A) activity. The phosphatidylinositol 3-kinase (PI3K) pathway further differentiated the regulation of these two enzymes, as inhibiting the PI3K pathway eliminated IFN-gamma induction of IDO, whereas such inhibition greatly enhanced WRS expression. These findings show discordance between modulations of expression of two distinct enzymes utilizing tryptophan as a common substrate, and raise the possibility of their involvement in regulating immune responses in various neurological disorders.en_US
dc.titleIFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4en_US
dc.typeJournal Articleen_US
cg.subject.ilriANIMAL DISEASESen_US
cg.identifier.statusLimited Accessen_US

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