Chronic rhinosinusitis and allergic rhinitis are chronic inflammatory diseases that affect the mucous membrane of the nose and paranasal sinuses. These diseases are characterized by recruitment of inflammatory cells t...Chronic rhinosinusitis and allergic rhinitis are chronic inflammatory diseases that affect the mucous membrane of the nose and paranasal sinuses. These diseases are characterized by recruitment of inflammatory cells to the upper airway. For this to take place a complex interaction between inflammatory cells and the cytokines/chemokines(ligand) liberated at the site of inflammation is involved in a process termed chemotaxis or directed cell migration against concentration gradient of the ligand. This entails signal transduction through the cell surface receptor resulting in cellular functional response and directed migration. In this editorial the novel role of CX3CR1 receptor in the immunopathology of chronic inflammation of the nose and paranasal sinuses will be explored with its potential role as therapeutic target in chronic nasal inflammation.展开更多
目的:探讨趋化因子受体CX3CR1对骨髓间充质干细胞(bone marrow-mesenchymal stem cells,BM-MSCs)修复受损肠上皮细胞的影响.方法:体外分离培养、鉴定BM-MSCs.采用肿瘤坏死因子-α(tumor necrosis factor a l p h a,T N F-α)处理结肠癌...目的:探讨趋化因子受体CX3CR1对骨髓间充质干细胞(bone marrow-mesenchymal stem cells,BM-MSCs)修复受损肠上皮细胞的影响.方法:体外分离培养、鉴定BM-MSCs.采用肿瘤坏死因子-α(tumor necrosis factor a l p h a,T N F-α)处理结肠癌上皮细胞(c o l o n adenocarcinoma epithelial cell line,Caco-2)建立肠上皮损伤模型.实验分为6组:(1)单纯BM-MSCs组;(2)单纯Caco-2组;(3)Caco-2+TNF-α组;(4)BM-MSCs+Caco-2组;(5)BMMSCs+Caco-2+TNF-α组;(6)anti-CX3CR1-BM-MSCs+Caco-2+TNF-α组,利用Transwell培养板将各组共培养,通过免疫荧光、We s t e r n b l o t及荧光定量RT-P C R方法检测Caco-2上ZO-1(zonula occluden 1)、Occludin和BM-MSCs上CX3CR1蛋白及mR NA表达水平.结果:选择100 ng/mL TNF-α处理Caco-2细胞48 h建立损伤模型后,检测ZO-1和Occludin表达水平明显降低(P<0.05).在BM-MSCs与未受损的Caco-2共培养时ZO-1、Occludin和CX3CR1蛋白及m RNA的表达不受影响,而在BM-MSCs与受损Caco-2共培养时,其表达增加(P<0.05).阻断CX3CR1后,ZO-1、Occludin蛋白及m RNA的表达与未阻断前相比明显减少(P<0.05).结论:CX3CR1参与BM-MSCs对受损肠上皮的修复.展开更多
The emission tomographic imaging of activated microglia in the brain moves into the focus of neuroscientific research with increasing recognition of contributions of early inflammatory processes to neurodegenerative, ...The emission tomographic imaging of activated microglia in the brain moves into the focus of neuroscientific research with increasing recognition of contributions of early inflammatory processes to neurodegenerative, traumatic, cancerous and infectious diseases of the brain. Whereas the mitochondrial isoform of the 18 kDa translocator protein (TSPO1) has been the main cellular target for positron emission tomography (PET) of this type of cells for decades, alternative marker proteins in the plasma membrane of microglia challenge efforts in ligand development, recently. The present report includes PET approaches using the chemokine receptor CX3CR1 and the FR2 folate receptor in parallel to small molecule PET tracers available for in vivo visualization of the “classical” target TSPO1. It compares first and second generation of TSPO1 ligands as well as new compounds like the tetrahydrocarbazole [18F]GE-180 and the quinazoline [11C]ER176 presumed to reduce polymorphism-related inter-subject variations, with allosteric ligands for the chemokine receptor CX3CR1 and with radio labelled folate conjugates targeting the folate “cargo” receptor FR1 and the FR2 receptor characteristic for anti-inflammatory M2 microglia.展开更多
文摘Chronic rhinosinusitis and allergic rhinitis are chronic inflammatory diseases that affect the mucous membrane of the nose and paranasal sinuses. These diseases are characterized by recruitment of inflammatory cells to the upper airway. For this to take place a complex interaction between inflammatory cells and the cytokines/chemokines(ligand) liberated at the site of inflammation is involved in a process termed chemotaxis or directed cell migration against concentration gradient of the ligand. This entails signal transduction through the cell surface receptor resulting in cellular functional response and directed migration. In this editorial the novel role of CX3CR1 receptor in the immunopathology of chronic inflammation of the nose and paranasal sinuses will be explored with its potential role as therapeutic target in chronic nasal inflammation.
文摘目的:探讨趋化因子受体CX3CR1对骨髓间充质干细胞(bone marrow-mesenchymal stem cells,BM-MSCs)修复受损肠上皮细胞的影响.方法:体外分离培养、鉴定BM-MSCs.采用肿瘤坏死因子-α(tumor necrosis factor a l p h a,T N F-α)处理结肠癌上皮细胞(c o l o n adenocarcinoma epithelial cell line,Caco-2)建立肠上皮损伤模型.实验分为6组:(1)单纯BM-MSCs组;(2)单纯Caco-2组;(3)Caco-2+TNF-α组;(4)BM-MSCs+Caco-2组;(5)BMMSCs+Caco-2+TNF-α组;(6)anti-CX3CR1-BM-MSCs+Caco-2+TNF-α组,利用Transwell培养板将各组共培养,通过免疫荧光、We s t e r n b l o t及荧光定量RT-P C R方法检测Caco-2上ZO-1(zonula occluden 1)、Occludin和BM-MSCs上CX3CR1蛋白及mR NA表达水平.结果:选择100 ng/mL TNF-α处理Caco-2细胞48 h建立损伤模型后,检测ZO-1和Occludin表达水平明显降低(P<0.05).在BM-MSCs与未受损的Caco-2共培养时ZO-1、Occludin和CX3CR1蛋白及m RNA的表达不受影响,而在BM-MSCs与受损Caco-2共培养时,其表达增加(P<0.05).阻断CX3CR1后,ZO-1、Occludin蛋白及m RNA的表达与未阻断前相比明显减少(P<0.05).结论:CX3CR1参与BM-MSCs对受损肠上皮的修复.
文摘The emission tomographic imaging of activated microglia in the brain moves into the focus of neuroscientific research with increasing recognition of contributions of early inflammatory processes to neurodegenerative, traumatic, cancerous and infectious diseases of the brain. Whereas the mitochondrial isoform of the 18 kDa translocator protein (TSPO1) has been the main cellular target for positron emission tomography (PET) of this type of cells for decades, alternative marker proteins in the plasma membrane of microglia challenge efforts in ligand development, recently. The present report includes PET approaches using the chemokine receptor CX3CR1 and the FR2 folate receptor in parallel to small molecule PET tracers available for in vivo visualization of the “classical” target TSPO1. It compares first and second generation of TSPO1 ligands as well as new compounds like the tetrahydrocarbazole [18F]GE-180 and the quinazoline [11C]ER176 presumed to reduce polymorphism-related inter-subject variations, with allosteric ligands for the chemokine receptor CX3CR1 and with radio labelled folate conjugates targeting the folate “cargo” receptor FR1 and the FR2 receptor characteristic for anti-inflammatory M2 microglia.
基金supported by the National Basic Research Program of China(No.2013CB531905)the National Natural Science Foundation of China(No.81571064)the National Basic Science Talent Cultivation Foundation of China(No.J1210041)