Inhibition of HDAC6 promotes microvascular endothelial cells to phagocytize myelin debris and reduces inflammatory response to accelerate the repair of spinal cord injury.

AIMS

To identify an effective strategy for promoting microvascular endothelial cells (MECs) to phagocytize myelin debris and reduce secretion of inflammatory factors following spinal cord injury (SCI).

METHODS

We established a coculture model of myelin debris and vascular-like structures. The efficiency with which MECs phagocytize myelin debris under different conditions was examined via ELISA, flow cytometry, and immunofluorescence. Tubastatin-A was used to interfere with the coculture model. The anti-inflammatory effects of Tubastatin-A were observed by HE staining, flow cytometry, immunofluorescence, and ELISA.

RESULTS

MECs phagocytized myelin debris via IgM opsonization, and phagocytosis promoted the secretion of inflammatory factors, whereas IgG-opsonized myelin debris had no effect on inflammatory factors. Application of the HDAC6 inhibitor Tubastatin-A increased the IgG levels and decreased the IgM levels by regulating the proliferation and differentiation of B cells. Tubastatin-A exerted a regulatory effect on the HDAC6-mediated autophagy-lysosome pathway, promoting MECs to phagocytize myelin debris, reducing the secretion of inflammatory factors, and accelerating the repair of SCI.

CONCLUSIONS

Inhibition of HDAC6 to regulate the immune-inflammatory response and promote MECs to phagocytize myelin debris may represent a novel strategy in the treatment of SCI.