FK506 Attenuates the Inflammation in Rat Spinal Cord Injury by Inhibiting the Activation of NF-κB in Microglia Cells
FK506 Attenuates the Inflammation in Rat Spinal Cord Injury by Inhibiting the Activation of NF-κB in Microglia Cells
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DOI：
10.1007/s10571-016-0422-8
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发表时间：
2017-07-01
影响因子：
4
通讯作者：
Zhao, Jianning
中科院分区：
文献类型：
--
作者：
Liu, Gang;Fan, Gentao;Zhao, Jianning
FK-506（他克莫司）是一种非常常用的免疫调节剂，在调节钙依赖性磷酸丝氨酸-磷酸苏氨酸蛋白磷酸酶钙调神经磷酸酶方面发挥重要作用，从而抑制钙调神经磷酸酶介导的继发性神经元损伤。FK-506在脊髓中的生物学功能尚未完全阐明。为了阐明FK-506在脊髓损伤（SCI）中的抗炎作用，我们在成年大鼠和低氧处理的原代脊髓小胶质细胞培养物中进行了急性脊髓挫伤模型。这项工作研究了NF-κ B和促炎细胞因子（TNF-α，IL-1b和IL-6）表达的激活。ELISA和q-PCR分析显示，脊髓挫伤后3天TNF-α、IL-1b和IL-6水平显著升高，14天后下降，同时伴有NF-κ B活化增加。这种增加被FK-506处理逆转。免疫荧光双标记提示NF-κ B B活化在小胶质细胞中尤为突出。免疫组化证实小胶质细胞的数量没有改变。此外，在低氧处理的原代脊髓小胶质细胞中的结果证实了FK-506对TNF-α、IL-1 B和IL-6表达以及NF-κ B活化的影响。这些结果表明，FK-506可能参与SCI后小胶质细胞的激活。
FK-506 (Tacrolimus) is a very commonly used immunomodulatory agent that plays important roles in modulating the calcium-dependent phosphoserine-phosphothreonine protein phosphatase calcineurin and thus inhibits calcineurin-mediated secondary neuronal damage. The biological function of FK-506 in the spinal cord has not been fully elucidated. To clarify the anti-inflammatory action of FK-506 in spinal cord injury (SCI), we performed an acute spinal cord contusion injury model in adult rats and hypoxia-treated primary spinal cord microglia cultures. This work studied the activation of NF-kappa B and proinflammatory cytokine (TNF-a, IL-1b, and IL-6) expression. ELISA and q-PCR analysis revealed that TNF-a, IL-1b, and IL-6 levels significantly increased 3 days after spinal cord contusion and decreased after 14 days, accompanied by the increased activation of NF-kappa B. This increase was reversed by an FK-506 treatment. Double immunofluorescence labeling suggested that NF-kappa B activation was especially prominent in microglia. Immunohistochemistry confirmed no alteration in the number of microglia. Moreover, the results in hypoxia-treated primary spinal cord microglia confirmed the effect of FK-506 on TNF-a, IL-1b, and IL-6 expression and NF-kappa B activation. These findings suggest that FK-506 may be involved in microglial activation after SCI.