IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4
Indoleamine 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...
| Autores principales: | , , , , , , |
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| Formato: | Journal Article |
| Lenguaje: | Inglés |
| Publicado: |
Wiley
2007
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| Materias: | |
| Acceso en línea: | https://hdl.handle.net/10568/1864 |
| _version_ | 1855524180387168256 |
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| author | Yadav, M.C. Burudi, E.M.E. Alirezaei, M. Flynn, C.C. Watry, D.D. Lanigan, C.M. Fox, H.S. |
| author_browse | Alirezaei, M. Burudi, E.M.E. Flynn, C.C. Fox, H.S. Lanigan, C.M. Watry, D.D. Yadav, M.C. |
| author_facet | Yadav, M.C. Burudi, E.M.E. Alirezaei, M. Flynn, C.C. Watry, D.D. Lanigan, C.M. Fox, H.S. |
| author_sort | Yadav, M.C. |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | Indoleamine 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. |
| format | Journal Article |
| id | CGSpace1864 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2007 |
| publishDateRange | 2007 |
| publishDateSort | 2007 |
| publisher | Wiley |
| publisherStr | Wiley |
| record_format | dspace |
| spelling | CGSpace18642023-09-09T12:45:33Z IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4 Yadav, M.C. Burudi, E.M.E. Alirezaei, M. Flynn, C.C. Watry, D.D. Lanigan, C.M. Fox, H.S. genetics animal diseases Indoleamine 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. 2007-10 2010-06-13T16:00:50Z 2010-06-13T16:00:50Z Journal Article https://hdl.handle.net/10568/1864 en Limited Access Wiley Yadav, 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. |
| spellingShingle | genetics animal diseases Yadav, M.C. Burudi, E.M.E. Alirezaei, M. Flynn, C.C. Watry, D.D. Lanigan, C.M. Fox, H.S. IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4 |
| title | IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4 |
| title_full | IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4 |
| title_fullStr | IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4 |
| title_full_unstemmed | IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4 |
| title_short | IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4 |
| title_sort | ifn gamma induced ido and wrs expression in microglia is differentially regulated by il 4 |
| topic | genetics animal diseases |
| url | https://hdl.handle.net/10568/1864 |
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