Effects of interferon-β on microglial functions as inflammatory and antigen presenting cells in the central nervous system
Effects of interferon-β on microglial functions as inflammatory and antigen presenting cells in the central nervous system
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DOI：
10.1016/j.neuropharm.2003.11.007
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发表时间：
2004-04-01
影响因子：
4.7
通讯作者：
Suzumura, A
中科院分区：
文献类型：
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作者：
Kawanokuchi, J;Mizuno, T;Suzumura, A
干扰素-β (IFNβ) 可减少复发缓解型多发性硬化症 (MS) 的恶化，但其发挥有益作用的确切机制尚不清楚。在这项研究中，我们检查了 IFNβ 对小胶质细胞功能的影响，作为炎症脱髓鞘的抗原呈递细胞或效应细胞。 IFNβ显着抑制小胶质细胞中II类MHC抗原和共刺激分子B7-1的表达。它还抑制小胶质细胞 IL-12 的产生以及髓鞘少突胶质细胞糖蛋白 (MOG) 致敏 T 细胞向 T 辅助细胞 I 表型的分化。使用小胶质细胞作为抗原呈递细胞。然而，IFNβ 显着且剂量依赖性地增强脱髓鞘炎症介质的产生，例如 TNFα、IL-11、1L-6 和一氧化氮 (NO)。磷酸二酯酶抑制剂可以有效抑制炎症介质的上调。因此，IFNβ可能在MS的诱导期发挥其抑制作用，但在效应期则不然。干扰素治疗的副作用可能是由于促炎细胞因子升高所致，并且可以通过与磷酸二酯酶抑制剂联合治疗来减少。 (C) 2004 Elsevier Ltd. 保留所有权利。
Interferon-beta (IFNbeta) reduces exacerbations of the relapsing-remitting form of multiple sclerosis (MS), but the exact mechanisms by which it exerts its beneficial effects are unknown. In this study, we examined the effects or IFNbeta on microglial functions, as either antigen presenting cells or effector cells for inflammatory demyelination. IFNbeta significantly suppressed the expression of class II MHC antigen and the co-stimulatory molecule B7-1 in microglia. It also suppressed microglial IL-12 production and differentiation of myelin oligodendrocyte glycoprotein (MOG)-sensitized T cells into the T helper I phenotype. which use microglia as antigen presenting cells. However, IFNbeta significantly and dose-dependently enhanced the production of inflammatory mediators for demyelination, such as TNFalpha, IL-11, 1L-6, and nitric oxide (NO). The upregulation of inflammatory mediators was effectively suppressed with a phosphodiesterase inhibitor. Thus, IFNbeta may exert its suppressive effects in the induction phase, but not in the effector phase of MS. Side effects of IFN treatment may be due to elevation of pro-inflammatory cytokines, and may be reduced by co-treatment with phosphodiesterase inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.