A hallmark of all forms of neurodegenerative diseases is impairment of neuronal functions,and in many cases neuronal cell death.Although the etiology of neurodegenerative diseases may be distinct,different diseases di...A hallmark of all forms of neurodegenerative diseases is impairment of neuronal functions,and in many cases neuronal cell death.Although the etiology of neurodegenerative diseases may be distinct,different diseases display a similar pathogenesis,for example abnormal immunity within the central nervous system(CNS),activation of macrophage/microglia and the involvement of proinflammatory cytokines.Recent studies show that neurons in a neurodegenerative state undergo a highly regulated programmed cell death,also called apoptosis.TNF-related apoptosis-inducing ligand(TRAIL),a member of the TNF family,has been shown to be involved in apoptosis during many diseases.As one member of a death ligand family,TRAIL was originally thought to target only tumor cells and was not present in CNS.However,recent data showed that TRAIL was unregulated in HIV-1-infected and immune-activated macrophages,a major disease inducing cell during HIV-1-assoeiated dementia(HAD).TRAIL is also induced on neuron by β-amyloid protein,an important pathogen for Alzheimer's disease.In this review,we summarize the possible common aspects that TRAIL involved those neurodegenerative diseases,TRAIL induced apoptosis signaling in the CNS cells,and specific role of TRAIL in individual diseases.Cellular & Molecular Immunology.2005;2(2):113-122.展开更多
Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are repo...Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are reported on the role of MIF in neurological recovery after ischemic stroke.The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF.Human neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL MIF recombinant(30 ng/mL)or ISO-1(MIF antagonist;50μM)was administered to human neuroblastoma cells.Then cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with MIF,OGD/R with ISO-1.Cell viability was analyzed using WST-1 assay.Expression levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity.WST-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group.Western blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group.Expression levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group.MIF administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R model.These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.展开更多
Macrophage death in advanced atherosclerosis promotes plaque necrosis and destabilization.Involvement of autophagy in bulk degradation of cellular components has been recognized recently as an important mechanism for ...Macrophage death in advanced atherosclerosis promotes plaque necrosis and destabilization.Involvement of autophagy in bulk degradation of cellular components has been recognized recently as an important mechanism for cell survival under endoplasmic reticulum（ER） stress.We previously found that the engagement of class A scavenger receptor（SR-A） triggered JNK-dependent apoptosis in ER-stressed macrophages.However,pro-apoptotic mechanisms mediated by SR-A are not fully understood.Therefore,we sought to see if SR-A mediated apoptosis was associated with autophagy in macrophages.Here,we showed that fucoidan inhibited microtubule-associated protein light chain 3-phospholipid conjugates（LC3-Ⅱ） formation as well as the number of autophagosomes under ER stress.The inhibition of LC3-Ⅱ formation was paralleled by the activation of the mTOR pathway,and the inhibition of mTOR allowed LC3-Ⅱ induction in macrophages treated with thapsigargin plus fucoidan.Furthermore,apoptosis induced by fucoidan was prevented under ER stress by the mTOR inhibitor.We propose that fucoidan,a SR-A agonist,may contribute to macrophage apoptosis during ER stress by inhibiting autophagy.展开更多
文摘A hallmark of all forms of neurodegenerative diseases is impairment of neuronal functions,and in many cases neuronal cell death.Although the etiology of neurodegenerative diseases may be distinct,different diseases display a similar pathogenesis,for example abnormal immunity within the central nervous system(CNS),activation of macrophage/microglia and the involvement of proinflammatory cytokines.Recent studies show that neurons in a neurodegenerative state undergo a highly regulated programmed cell death,also called apoptosis.TNF-related apoptosis-inducing ligand(TRAIL),a member of the TNF family,has been shown to be involved in apoptosis during many diseases.As one member of a death ligand family,TRAIL was originally thought to target only tumor cells and was not present in CNS.However,recent data showed that TRAIL was unregulated in HIV-1-infected and immune-activated macrophages,a major disease inducing cell during HIV-1-assoeiated dementia(HAD).TRAIL is also induced on neuron by β-amyloid protein,an important pathogen for Alzheimer's disease.In this review,we summarize the possible common aspects that TRAIL involved those neurodegenerative diseases,TRAIL induced apoptosis signaling in the CNS cells,and specific role of TRAIL in individual diseases.Cellular & Molecular Immunology.2005;2(2):113-122.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.2016R1A2B4012772(to DYK)
文摘Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are reported on the role of MIF in neurological recovery after ischemic stroke.The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF.Human neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL MIF recombinant(30 ng/mL)or ISO-1(MIF antagonist;50μM)was administered to human neuroblastoma cells.Then cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with MIF,OGD/R with ISO-1.Cell viability was analyzed using WST-1 assay.Expression levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity.WST-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group.Western blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group.Expression levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group.MIF administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R model.These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.
基金supported by the National Basic Research Program(973) Grant(No.2012CB517503 and No.2011CB503903)National Natural Science Foundation of China(No.81230070 and No. 81070120) to Qi Chen+1 种基金the National Natural Science Foundation of China Grant(No.81000118) to Jingjing Benthe National Natural Science Foundation of China Grant(No.81100857) to Xiaoyu Li
文摘Macrophage death in advanced atherosclerosis promotes plaque necrosis and destabilization.Involvement of autophagy in bulk degradation of cellular components has been recognized recently as an important mechanism for cell survival under endoplasmic reticulum（ER） stress.We previously found that the engagement of class A scavenger receptor（SR-A） triggered JNK-dependent apoptosis in ER-stressed macrophages.However,pro-apoptotic mechanisms mediated by SR-A are not fully understood.Therefore,we sought to see if SR-A mediated apoptosis was associated with autophagy in macrophages.Here,we showed that fucoidan inhibited microtubule-associated protein light chain 3-phospholipid conjugates（LC3-Ⅱ） formation as well as the number of autophagosomes under ER stress.The inhibition of LC3-Ⅱ formation was paralleled by the activation of the mTOR pathway,and the inhibition of mTOR allowed LC3-Ⅱ induction in macrophages treated with thapsigargin plus fucoidan.Furthermore,apoptosis induced by fucoidan was prevented under ER stress by the mTOR inhibitor.We propose that fucoidan,a SR-A agonist,may contribute to macrophage apoptosis during ER stress by inhibiting autophagy.
