Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
Background The form deprivation （FD） reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate （cGMP） are involved in visual signal transmission. This study investigated changes...Background The form deprivation （FD） reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate （cGMP） are involved in visual signal transmission. This study investigated changes in nitric oxide synthase （NOS） activity and cGMP concentration in ocular tissues in acute and chronic form deprivation myopia. Methods Guinea pigs had one eye covered by translucent glass for 7, 14 or 21 days. Untreated litter mates were used as controls. NOS activity and cGMP concentrations in the retinal, choroidal and scleral tissues of FD eyes and control eyes were analyzed by radioimmunoassay after various durations of FD. The expression of NOS subtypes was identified by immunohistochemistry. Results Myopia was successfully induced in FD eyes after 14 days. Compared with control groups, the retinal NOS activity and cGMP concentrations in the FD eyes significantly increased after 14 and 21 days while the retinal NOS activity in the FD eyes was transiently suppressed by 7 days of FD. The NOS activity and cGMP concentrations of choroid and sclera in the FD eyes were higher than in the control groups at 21 days. The three isoenzymes of nitric oxide synthase were detected in the ocular tissues of guinea pigs. Conclusions The NOS activity and cGMP concentrations were upregulated after chronic FD and the retinal NOS activity was transiently suppressed at acute FD. The function of elevated NOS activity may be mediated by cGMP.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金This work was supported by a grant from the National Nature Science Foundation of China(No.C30572005)
文摘Background The form deprivation （FD） reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate （cGMP） are involved in visual signal transmission. This study investigated changes in nitric oxide synthase （NOS） activity and cGMP concentration in ocular tissues in acute and chronic form deprivation myopia. Methods Guinea pigs had one eye covered by translucent glass for 7, 14 or 21 days. Untreated litter mates were used as controls. NOS activity and cGMP concentrations in the retinal, choroidal and scleral tissues of FD eyes and control eyes were analyzed by radioimmunoassay after various durations of FD. The expression of NOS subtypes was identified by immunohistochemistry. Results Myopia was successfully induced in FD eyes after 14 days. Compared with control groups, the retinal NOS activity and cGMP concentrations in the FD eyes significantly increased after 14 and 21 days while the retinal NOS activity in the FD eyes was transiently suppressed by 7 days of FD. The NOS activity and cGMP concentrations of choroid and sclera in the FD eyes were higher than in the control groups at 21 days. The three isoenzymes of nitric oxide synthase were detected in the ocular tissues of guinea pigs. Conclusions The NOS activity and cGMP concentrations were upregulated after chronic FD and the retinal NOS activity was transiently suppressed at acute FD. The function of elevated NOS activity may be mediated by cGMP.
