Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most commo...Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most common disabling neurological disease in young adulthood.展开更多
目的研究丙酮酸乙酯对大鼠冠状动脉微栓塞后炎症因子表达的影响。方法通过心尖部注射大鼠自体血栓微粒建立大鼠冠状动脉微栓塞模型。36只大鼠分为假手术组、冠状动脉微栓塞未治疗组和丙酮酸乙酯预处理组,每组各12只,于术后3天处死。W es...目的研究丙酮酸乙酯对大鼠冠状动脉微栓塞后炎症因子表达的影响。方法通过心尖部注射大鼠自体血栓微粒建立大鼠冠状动脉微栓塞模型。36只大鼠分为假手术组、冠状动脉微栓塞未治疗组和丙酮酸乙酯预处理组,每组各12只,于术后3天处死。W estern b lot测定肿瘤坏死因子α、白细胞介素1β的表达水平,实时PCR检测肿瘤坏死因子α、白细胞介素1βmRNA表达量。结果与假手术组相比,冠状动脉微栓塞后3天,心肌组织肿瘤坏死因子α、白细胞介素1βmRNA及蛋白水平明显升高;左室功能显著恶化,左室舒张末压明显增大,左室收缩压、左室内压上升最大速率明显下降(P<0.01);心肌肿瘤坏死因子α、白细胞介素1β蛋白水平与心功能呈明显相关性。与冠状动脉微栓塞未治疗组比较,丙酮酸乙酯预处理能够显著抑制冠状动脉微栓塞后肿瘤坏死因子α、白细胞介素1β的mRNA及蛋白水平表达,改善心室功能。结论丙酮酸乙酯预处理能够抑制大鼠冠状动脉微栓塞后促炎症因子的过度激活,改善心功能。展开更多
During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like recept...During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like receptors,and nucleotide-binding and oligomerization domain-like receptors.The binding of the pathogen-derived nucleic acids to their corresponding sensors initiates certain downstream signaling cascades culminating in the release of type-I interferons(IFNs),especially IFN-αand other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the host.Although these sensors are hardwired to recognize pathogen associated molecular patterns,like viral and bacterial nucleic acids,under unusual physiological conditions,such as excessive cellular stress and increased apoptosis,endogenous self-nucleic acids like DNA,RNA,and mitochondrial DNA are also released.The presence of these self-nucleic acids in extranuclear compartments or extracellular spaces or their association with certain proteins sometimes leads to the failure of discriminating mechanisms of nucleic acid sensors leading to proinflammatory responses as seen in autoimmune disorders,like systemic lupus erythematosus,psoriasis and to some extent in type 1 diabetes(T1D).This review discusses the involvement of various nucleic acid sensors in autoimmunity and discusses how aberrant recognition of self-nucleic acids by their sensors activates the innate immune responses during the pathogenesis of T1D.展开更多
Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, wheth...Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, whether Toll-like receptor 4 is expressed by primary cultured hippocampal neurons and its specific role in lipopolysaccharide-induced neuroinflammation is currently undefined, in this study, Toll-like receptor 4 antibody blocking was used to analyze the Toll-like receptor 4 signaling pathway and changes in inflammation of lipopolysaccharide stimulated hippocampal neurons. Immunofluorescence showed that Toll-like receptor 4 protein was mainly located in the membrane of hippocampal neurons. Quantitative reverse transcription-PCR and western blot assay showed that after stimulation of lipopolysaccharide, the mRNA and protein levels of Toll-like receptor 4 and the mRNA levels of interleukin-ll3 and tumor necrosis factor-（] were significantly increased. In addition, there was increased phosphorylation and degradation of kappa B a inhibitor in the cytosol and increased nuclear factor-KB p65 expression in the nuclei. Pretreatment with Toll-like receptor 4 antibody could almost completely block this increase. These experimental findings indicate that lipopolysaccharide participates in neuroinflammation by stimulating Toll-like receptor 4/nuclear factor-KB pathway in hippocampal neurons, which may be both ＂passive victims＂ and ＂activators＂ of neuroinflammation.展开更多
基金Dr.Mao-Draayer has served as a consultant and/or received grant support from:Acorda,Bayer Pharmaceutical,Biogen Idec,EMD Serono,Genzyme,Novartis,Questor,Teva Neuroscience and Chugai PharmaDr.Mao-Draayeris currently supported by grants from NIH NIAID Autoimmune Center of Excellence:UM1-AI110557+1 种基金NIH NINDS R01-NS080821the University of Michigan Neurology Department
文摘Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most common disabling neurological disease in young adulthood.
文摘目的研究丙酮酸乙酯对大鼠冠状动脉微栓塞后炎症因子表达的影响。方法通过心尖部注射大鼠自体血栓微粒建立大鼠冠状动脉微栓塞模型。36只大鼠分为假手术组、冠状动脉微栓塞未治疗组和丙酮酸乙酯预处理组,每组各12只,于术后3天处死。W estern b lot测定肿瘤坏死因子α、白细胞介素1β的表达水平,实时PCR检测肿瘤坏死因子α、白细胞介素1βmRNA表达量。结果与假手术组相比,冠状动脉微栓塞后3天,心肌组织肿瘤坏死因子α、白细胞介素1βmRNA及蛋白水平明显升高;左室功能显著恶化,左室舒张末压明显增大,左室收缩压、左室内压上升最大速率明显下降(P<0.01);心肌肿瘤坏死因子α、白细胞介素1β蛋白水平与心功能呈明显相关性。与冠状动脉微栓塞未治疗组比较,丙酮酸乙酯预处理能够显著抑制冠状动脉微栓塞后肿瘤坏死因子α、白细胞介素1β的mRNA及蛋白水平表达,改善心室功能。结论丙酮酸乙酯预处理能够抑制大鼠冠状动脉微栓塞后促炎症因子的过度激活,改善心功能。
文摘During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like receptors,and nucleotide-binding and oligomerization domain-like receptors.The binding of the pathogen-derived nucleic acids to their corresponding sensors initiates certain downstream signaling cascades culminating in the release of type-I interferons(IFNs),especially IFN-αand other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the host.Although these sensors are hardwired to recognize pathogen associated molecular patterns,like viral and bacterial nucleic acids,under unusual physiological conditions,such as excessive cellular stress and increased apoptosis,endogenous self-nucleic acids like DNA,RNA,and mitochondrial DNA are also released.The presence of these self-nucleic acids in extranuclear compartments or extracellular spaces or their association with certain proteins sometimes leads to the failure of discriminating mechanisms of nucleic acid sensors leading to proinflammatory responses as seen in autoimmune disorders,like systemic lupus erythematosus,psoriasis and to some extent in type 1 diabetes(T1D).This review discusses the involvement of various nucleic acid sensors in autoimmunity and discusses how aberrant recognition of self-nucleic acids by their sensors activates the innate immune responses during the pathogenesis of T1D.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Nantong Applied Research Program,No.k2010036+1 种基金the 2011 Jiangsu Graduated Students' Research and Innovation Program,No.CX2211-0640the Nantong University Graduated Students' Technological and Innovative Program,No.YKC11033
文摘Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, whether Toll-like receptor 4 is expressed by primary cultured hippocampal neurons and its specific role in lipopolysaccharide-induced neuroinflammation is currently undefined, in this study, Toll-like receptor 4 antibody blocking was used to analyze the Toll-like receptor 4 signaling pathway and changes in inflammation of lipopolysaccharide stimulated hippocampal neurons. Immunofluorescence showed that Toll-like receptor 4 protein was mainly located in the membrane of hippocampal neurons. Quantitative reverse transcription-PCR and western blot assay showed that after stimulation of lipopolysaccharide, the mRNA and protein levels of Toll-like receptor 4 and the mRNA levels of interleukin-ll3 and tumor necrosis factor-（] were significantly increased. In addition, there was increased phosphorylation and degradation of kappa B a inhibitor in the cytosol and increased nuclear factor-KB p65 expression in the nuclei. Pretreatment with Toll-like receptor 4 antibody could almost completely block this increase. These experimental findings indicate that lipopolysaccharide participates in neuroinflammation by stimulating Toll-like receptor 4/nuclear factor-KB pathway in hippocampal neurons, which may be both ＂passive victims＂ and ＂activators＂ of neuroinflammation.
