Interleukin-1 participates in the classical and alternative activation of microglia/macrophages after spinal cord injury.
Interleukin-1 participates in the classical and alternative activation of microglia/macrophages after spinal cord injury.
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DOI：
10.1186/1742-2094-9-65
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发表时间：
2012-04-07
影响因子：
9.3
通讯作者：
Shioda S
中科院分区：
文献类型：
--
作者：
Sato A;Ohtaki H;Tsumuraya T;Song D;Ohara K;Asano M;Iwakura Y;Atsumi T;Shioda S
小胶质细胞和巨噬细胞(MG/MΦ)根据独特的细胞因子刺激具有不同的功能，并在中枢神经系统疾病中参与神经细胞的死亡、修复和重塑。虽然IL-1已被证明可以加剧炎症，但它也被认为可以促进神经再生。在IL-1基因敲除(KO)小鼠的脊髓损伤(SCI)模型中，我们检测了MG/MΦ的激活表型以及IL-1对其的影响。此外，我们使用成人MG原代培养细胞，在体外证明了IL-1对MG经典激活和交替激活的贡献。在野生型和IL-1KO小鼠中，横断T9和T10椎体之间的脊髓造成脊髓损伤。连续14天监测患者的运动能力并确定病变大小。监测肿瘤坏死因子α和YM1水平以确定MG/MΦ的激活表型。MG原代培养取自成年小鼠，分别加入干扰素γ或IL-4加或不加IL-1β。此外，在存在和不存在IL-1β的情况下，将培养物暴露于IL-4和/或IL-13。与野生型小鼠相比，IL-1KO小鼠脊髓损伤后的运动能力和损伤面积明显改善。IL-1KO小鼠肿瘤坏死因子α的产生受到明显抑制。此外，另一种激活MG/MΦ的标志物YM1在IL-1KO小鼠中未见增加，提示IL-1参与了MG/MΦ的经典激活和交替激活。我们用干扰素γ或IL-4处理原代培养的MG细胞，同时加入和不加IL-1β。经干扰素α和IL-1γ共同作用后，培养上清液中一氧化氮和肿瘤坏死因子β表达增加，细胞悬液中诱导型一氧化氮合酶表达增加。IL-4作用后，交替激活标志物YM1和精氨酸酶-1的表达增加，经IL-4和IL-1β联合处理后，其表达进一步增加。细胞暴露于IL-13后，未观察到表型。在活体实验中，我们证明了IL-1通过减少炎症反应来抑制脊髓损伤。此外，我们认为，在体内和体外系统中，IL-1都参与了MG的经典激活和交替激活。
Microglia and macrophages (MG/MΦ) have a diverse range of functions depending on unique cytokine stimuli, and contribute to neural cell death, repair, and remodeling during central nervous system diseases. While IL-1 has been shown to exacerbate inflammation, it has also been recognized to enhance neuroregeneration. We determined the activating phenotype of MG/MΦ and the impact of IL-1 in an in vivo spinal cord injury (SCI) model of IL-1 knock-out (KO) mice. Moreover, we demonstrated the contribution of IL-1 to both the classical and alternative activation of MG in vitro using an adult MG primary culture. SCI was induced by transection of the spinal cord between the T9 and T10 vertebra in wild-type and IL-1 KO mice. Locomotor activity was monitored and lesion size was determined for 14 days. TNFα and Ym1 levels were monitored to determine the MG/MΦ activating phenotype. Primary cultures of MG were produced from adult mice, and were exposed to IFNγ or IL-4 with and without IL-1β. Moreover, cultures were exposed to IL-4 and/or IL-13 in the presence and absence of IL-1β. The locomotor activity and lesion area of IL-1 KO mice improved significantly after SCI compared with wild-type mice. TNFα production was significantly suppressed in IL-1 KO mice. Also, Ym1, an alternative activating MG/MΦ marker, did not increase in IL-1 KO mice, suggesting that IL-1 contributes to both the classical and alternative activation of MG/MΦ. We treated primary MG cultures with IFNγ or IL-4 in the presence and absence of IL-1β. Increased nitric oxide and TNFα was present in the culture media and increased inducible NO synthase was detected in cell suspensions following co-treatment with IFNγ and IL-1β. Expression of the alternative activation markers Ym1 and arginase-1 was increased after exposure to IL-4 and further increased after co-treatment with IL-4 and IL-1β. The phenotype was not observed after exposure of cells to IL-13. We demonstrate here in in vivo experiments that IL-1 suppressed SCI in a process mediated by the reduction of inflammatory responses. Moreover, we suggest that IL-1 participates in both the classical and alternative activation of MG in in vivo and in vitro systems.
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影响因子：
2.8
作者：
Knoller, N;Auerbach, G;Hadani, M
通讯作者：
Hadani, M
影响因子：
9.3
作者：
Dohi K;Ohtaki H;Nakamachi T;Yofu S;Satoh K;Miyamoto K;Song D;Tsunawaki S;Shioda S;Aruga T
通讯作者：
Aruga T
影响因子：
2.5
作者：
Inman, DM;Steward, O
通讯作者：
Steward, O
他莫昔芬通过减弱体外和体内小胶质细胞炎症反应来减轻辐射引起的脑损伤
影响因子：
2.9
作者：
Liu, Jun-Li;Tian, Dai-Shi;Wu, Gang
通讯作者：
Wu, Gang
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG