title: 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: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors: Gang
authors: G
authors: Liu
authors: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors: Gentao
authors: G
authors: Fan
authors: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors: Guodong
authors: G
authors: Guo
authors: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors: Wenbo
authors: W
authors: Kang
authors: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors: Dongsheng
authors: D
authors: Wang
authors: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors: Bin
authors: B
authors: Xu
authors: Department of Orthopedic Surgery, Jinling Hospital, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu, China. jqzyliugang@163.com.
authors: Jianning
authors: J
authors: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D000860:Hypoxia / Q000150:complications / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D016559:Tacrolimus
keywords: FK-506; Microglia; NF-κB; Proinflammatory cytokines; Rat; Spinal cord injury