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

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.

• Authors: Gang Liu, Gentao Fan, Guodong Guo, Wenbo Kang, Dongsheng Wang, Bin Xu, Jianning Zhao
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 37 Issue 5 Pg. 843-855 (Jul 2017) ISSN: 1573-6830 [Electronic] United States
• PMID: 27572744 (Publication Type: Journal Article)

Chemical References

• CD11b Antigen
• Cytokines
• Inflammation Mediators
• NF-kappa B
• Tacrolimus

Topics

• Animals
• Apoptosis (drug effects)
• CD11b Antigen (metabolism)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cytokines (metabolism)
• Hypoxia (complications, pathology)
• Inflammation (complications, drug therapy, pathology)
• Inflammation Mediators (metabolism)
• Male
• Microglia (metabolism, pathology)
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Rats, Sprague-Dawley
• Spinal Cord (pathology)
• Spinal Cord Injuries (complications, drug therapy, pathology)
• Tacrolimus (pharmacology, therapeutic use)