Inhibition of HDAC6 promotes microvascular endothelial cells to phagocytize myelin debris and reduces inflammatory response to accelerate the repair of spinal cord injury
Inhibition of HDAC6 promotes microvascular endothelial cells to phagocytize myelin debris and reduces inflammatory response to accelerate the repair of spinal cord injury
复制标题
DOI：
10.1111/cns.14439
复制
发表时间：
2023-08-29
影响因子：
5.5
通讯作者：
Guo，Yang
中科院分区：
文献类型：
--
作者：
Wu，Chengjie;Pan，Yalan;Guo，Yang
目的探讨脊髓损伤（spinal cord injury，SCI）后促进微血管内皮细胞（microvascular endothelial cells，MEC）吞噬髓鞘碎片、减少炎症因子分泌的有效策略。通过ELISA、流式细胞术和免疫荧光检测MECs在不同条件下吞噬髓鞘碎片的效率。使用Tubastatin‐A干扰共培养模型。采用HE染色、流式细胞术、免疫荧光和ELISA等方法观察Tubastatin‐A的抗炎作用。结果MEC通过IgM调理作用吞噬髓鞘碎片，并促进炎症因子的分泌，而IgG调理的髓鞘碎片对炎症因子无影响。HDAC 6抑制剂Tubastin-A的应用通过调节B细胞的增殖和分化来增加IgG水平并降低IgM水平。Tubastin-A对HDAC 6介导的自噬-溶酶体通路发挥调节作用，促进MEC吞噬髓鞘碎片，减少炎症因子的分泌，加速SCI的修复。结论抑制HDAC 6调节免疫炎症反应，促进MEC吞噬髓鞘碎片，可能是SCI治疗的新策略。
AimsTo 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).MethodsWe 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.ResultsMECs 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.ConclusionsInhibition 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.