S100-Beta Aggravates Spinal Cord Injury Via Activation Of M1 Macrophage Phenotype

Objectives: S100-beta has been identified as a sensitive biomarker in central nervous system injuries. However, the functions and mechanisms of S100-beta are unknown in spinal cord injury. Methods: Spinal cord injury (SCI) mouse model was generated by surgical operation, microglia activation model was established by inducing BV-2 cells with LPS. The SCI model was evaluated by Basso-Beattie-Bresnahan (BBB) behavioral score, HE staining, and Nissl staining. The expression level of S100-beta was detected by qRT-PCR, western blot. and immunofluorescence. qRT-PCR and western blot were used to detect the expression of iNOS and CD16. Pro-inflammatory cytokines TNF-alpha and IL-1 beta levels were detected by qRT-PCR and ELISA. Results: The expression of IL-1 beta, TNF-alpha, iNOS, and CD16 increased at 3rd day after SCI. In BV2 microglia, LPS treatment promoted the expression of S100-beta, IL-1 beta, TNF-alpha, iNOS, and CD16. Knockdown of 5100-13 reduced the expression of iNOS stimulated by LPS. Over-expression of S100-13 increased IL-1 beta and TNF-alpha, and S100-beta inhibition suppressed IL-1 beta and INF-alpha. In SCI mice, knockdown of S100-beta attenuated the spinal cord injury and inhibited the expression of iNOS, IL-1 beta, and TNF-alpha. Conclusions: Down-regulation of S100-beta could inhibit the pathogenesis of SCI and inhibit the activation of M1 macrophages. S100-beta may be a useful diagnostic biomarker or therapeutic target for SCI.