Downregulation of miR-199b promotes the acute spinal cord injury through IKKβ-NF-κB signaling pathway activating microglial cells

Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and NB kinase ()nuclear factor-kappa B (IKK beta-NF-kappa B) signaling pathway were evaluated by quantitative reverse transcriptionPCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of 1KK beta-NF-kappa B were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKK beta by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKK beta, p-p65, tumor necrosis factor-a (TNF-alpha) and interleukin-1 beta (IL-beta) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-a and IL-1 beta. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKK beta-NF-kappa B signaling pathway and TNF-a and IL-1 beta. These results indicated that miR-199b attenuated ASCI at least partly through IKK beta-NF-kappa B signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.