Abstract
BackgroundSpinal cord injury (SCI) is a severe traumatic injury that often leads to paralysis. The neuroinflammation following SCI plays an important role during the secondary injury phase. C-C motif chemokine ligand 20 (CCL20) works like a magnet to attract inflammatory cells and subsequently regulate inflammation. However, the role and mechanisms of CCL20 in neuroinflammation following traumatic injury are poorly understood.MethodsA modified Allen’s weight drop method was applied to induce a rat moderate contusion injury model. HE staining was used to assess spinal cord histopathology, and the water content test was used to estimate spinal cord edema. Motor function scores were quantified to evaluate locomotor ability, and leukocyte infiltration was observed by CD45 immunofluorescence and flow cytometry. Additionally, qRT-PCR and ELISA were used to determine inflammatory mediator gene expression. Th17 cell recruitment was identified by flow cytometry.ResultsCompared with the injury control groups, histological analysis of the lesion area and tissue edema revealed reduced spinal cord edema and decreased lesion volume in the group administrated with CCL20 neutralizing antibody. Locomotor activity, as assessed by Basso, Beattie, and Bresnahan (BBB) score, showed that CCL20 blockade was beneficial for motor function recovery. Results also showed that leukocyte infiltration was reduced by neutralizing CCL20 at 7 days post-injury. More importantly, expression levels of IL-1β, IL-6, and TNF-α at 24 h after SCI demonstrated that a reduced inflammatory reaction in the CCL20 antibody group compared with the injury controls. Although CCL20 altered the expression of IL-1β, IL-6, and TNF-α, it had no effect on anti-inflammatory IL-10 expression at 24 h after damage. Notably, tissue flow cytometry confirmed that Th17 cell recruitment in the CCL20 antibody group was decreased compared with the control groups at 14 days post-injury. Additionally, IL-17A expression, which is mainly secreted by Th17 cell, suggested that CCL20 blockade also reduced IL-17A levels at 14 days after SCI.ConclusionsThese results suggested that CCL20 aggravates neuroinflammation following SCI via regulation of Th17 cell recruitment and IL-17A level. Thus, CCL20-target therapy could be a promising clinical application for the treatment of SCI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0630-7) contains supplementary material, which is available to authorized users.
Highlights
Spinal cord injury (SCI) is a severe traumatic injury that often leads to paralysis
C motif chemokine ligand 20 (CCL20) monoclonal neutralizing antibody may persist for the entire period of expression in the spinal cord, as determined by quantitative real-time polymerase chain reaction (qRT-PCR), shows that SCI leads to increased CCL20 mRNA level in the spinal cord, especially during the early period of SCI. b Mouse IgG levels of rat serum, as determined by enzyme-linked immunosorbent assay (ELISA), are significantly increased in CCL20 monoclonal antibody (mAb) group and isotype control group from 6 h to 28 days post-SCI
CCL20 immunostaining at 1 day post-injury in the sham group (c), SCI group (d), negative control of the sham group (e), and negative control of the SCI group (f) indicates that CCL20 is mainly localized in the cytoplasm of gray matter neurons and glial cells
Summary
Spinal cord injury (SCI) is a severe traumatic injury that often leads to paralysis. Following disruption of the blood-spinal cord barrier, an influx of inflammatory cells and a strong expression of inflammatory mediators induce a reactive process of secondary cell death in tissue surrounding the original injury site [5, 6]. This inflammatory reaction continues for days or weeks and could lead to cavitation and formation of a glial scar, thereby exacerbating neurological dysfunction
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