Distinct roles of IFNβ and IFNγ in the production of proinflammatory and antiinflammatory cytokines in bone marrow-derived dendritic cells (BA12P.109)
| Autor: | Jui-Hung Yen, Weimin Kong, Kirsten Hooper, Ping-Chang Kuo, Doina Ganea |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:176.10-176.10 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | IFNβ and IFNγ play distinct roles in MS/EAE. IFNγ exacerbates whereas IFNβ ameliorates the disease of EAE. Dendritic cells (DC) paly a sentinel role in the immune system, and are recruited to the CNS to restimulate encephalitogenic T cells during the course of EAE. We investigate how DC are regulated differently by IFNβ and IFNγ on the production of proinflammatory cytokines IL-12 and IL-23 and of antiinflammatory cytokine IL-10. Moreover, the molecular mechanisms of IFNβ and IFNγ-mediated regulatory effects are also investigated. Our results show IFNβ inhibited the production of IL-12 and IL-23, whereas enhanced the production of IL-10 in activated DC. Although both IFNβ and IFNγ inhibited IL-23 production, IFNγ enhanced IL-12 but suppressed IL-10 production. IFNγ-induced STAT-1/IRF-1 activation is required for IL-12 upregulation and IL-23 downregulation. Although STAT-1 activation is responsible for IFNγ-mediated IL-10 downregulation, IRF-1 activation is not involved in STAT-1-mediated IL-10 downregulation. Similar to IFNγ, IFNβ induced STAT-1 activation to suppress IL-23 production, however, the effect is independent of IRF-1 activation. IFNβ-induced Akt activation and GSK3β inactivation might be responsible for IL-12 downregulation and IL-10 upregulation as GSK3β activation is linked to inflammatory responses. In conclusion, our results provide the molecular mechanisms by which IFNβ and IFNγ utilize distinct signaling pathways to regulate the cytokine productions in DCs. |
| Databáze: | OpenAIRE |
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