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FK506 Attenuates the Inflammation in Rat Spinal Cord Injury by Inhibiting the Activation of NF-κB in Microglia Cells

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Abstract

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-κB 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-κB. This increase was reversed by an FK-506 treatment. Double immunofluorescence labeling suggested that NF-κB 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-κB activation. These findings suggest that FK-506 may be involved in microglial activation after SCI.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China

    Gang Liu, Gentao Fan, Guodong Guo, Wenbo Kang, Dongsheng Wang, Bin Xu & Jianning Zhao

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  1. Gang Liu
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  2. Gentao Fan
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  3. Guodong Guo
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  4. Wenbo Kang
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  5. Dongsheng Wang
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  7. Jianning Zhao
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Correspondence to Jianning Zhao.

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Liu, G., Fan, G., Guo, G. et al. FK506 Attenuates the Inflammation in Rat Spinal Cord Injury by Inhibiting the Activation of NF-κB in Microglia Cells. Cell Mol Neurobiol 37, 843–855 (2017). https://doi.org/10.1007/s10571-016-0422-8

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