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 pat...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.展开更多
BACKGROUND Transverse myelitis(TM)is characterized by sudden lower extremity progressive weakness and sensory impairment,and most patients have a history of advanced viral infection symptoms.A variety of disorders can...BACKGROUND Transverse myelitis(TM)is characterized by sudden lower extremity progressive weakness and sensory impairment,and most patients have a history of advanced viral infection symptoms.A variety of disorders can cause TM in association with viral or nonviral infection,vascular,neoplasia,collagen vascular,and iatrogenic,such as vaccination.Vaccination has become common through the global implementation against coronavirus disease 2019(COVID-19)and reported complications like herpes zoster(HZ)activation has increased.CASE SUMMARY This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine(Oxford/AstraZeneca([ChAdOx1S{recombinant}]).The patient had a paraplegia aggravation 3 wk after HZ symptoms started.Spinal magnetic resonance imaging(MRI)showed transverse myelitis at the T6–T9 Level.Treatment was acyclovir with steroids combined with physical therapy.Her neurological function was slowly restored by Day 17.CONCLUSION HZ developed after COVID-19 vaccination,which may lead to more severe complications.Therefore,HZ treatment itself should not be delayed.If neurological complications worsen after appropriate management,an immediate diagnostic procedure,such as magnetic resonance imaging and laboratory tests,will start and should treat the neurological complications.展开更多
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).
文摘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.
基金Supported by Research fund from Chosun University Hospital,2022.
文摘BACKGROUND Transverse myelitis(TM)is characterized by sudden lower extremity progressive weakness and sensory impairment,and most patients have a history of advanced viral infection symptoms.A variety of disorders can cause TM in association with viral or nonviral infection,vascular,neoplasia,collagen vascular,and iatrogenic,such as vaccination.Vaccination has become common through the global implementation against coronavirus disease 2019(COVID-19)and reported complications like herpes zoster(HZ)activation has increased.CASE SUMMARY This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine(Oxford/AstraZeneca([ChAdOx1S{recombinant}]).The patient had a paraplegia aggravation 3 wk after HZ symptoms started.Spinal magnetic resonance imaging(MRI)showed transverse myelitis at the T6–T9 Level.Treatment was acyclovir with steroids combined with physical therapy.Her neurological function was slowly restored by Day 17.CONCLUSION HZ developed after COVID-19 vaccination,which may lead to more severe complications.Therefore,HZ treatment itself should not be delayed.If neurological complications worsen after appropriate management,an immediate diagnostic procedure,such as magnetic resonance imaging and laboratory tests,will start and should treat the neurological complications.
