Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis  

作　　者：Chunyun Liu Shangde Guo Rong Liu Minfang Guo Qing Wang Zhi Chai Baoguo Xiao Cungen Ma 

机构地区：[1]Institute of Brain Science,Shanxi Datong University,Datong,Shanxi Province,China [2]The Key Research Laboratory of Benefiting Qi for Acting Blood Cireulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology,Shanxi University of Chinese Medicine,Taiyuan,Shanxi Province,China [3]Institute of Neurology,Huashan Hospital,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai,China

出　　处：《Neural Regeneration Research》2024年第3期671-679,共9页中国神经再生研究（英文版）

基　　金：supported by a grant from the Department of Science and Technology of Shanxi Province,China,No.20210302123477(to CL);Datong Bureau of Science and Technology of China,No.2020152(to CL);the Opening Foundation of Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine,No.2022-KF-03(to CL).

摘　　要：Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

关 键 词：ANTI-INFLAMMATORY experimental autoimmune encephalomyelitis FASUDIL macrophage multiple sclerosis PRO-INFLAMMATORY Rho kinase 

分 类 号：R744.3[医药卫生—神经病学与精神病学]