Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C（IL-17RC）,a phenomenon observed in peripheral blood and chorioretinal tissues with age-rela...Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C（IL-17RC）,a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration（AMD）,was associated with altered activation of phosphatidylinositide 3-kinase（PI3K）,Akt,and glycogen synthase kinase 3（GSK3）.We wondered whether or not altered PI3 K,Akt,and GSK3 activities could be detected in peripheral blood mononuclear cells（PBMC） obtained from AMD patients.In the patients＇ PBMC,absent or reduced serine-phosphorylation of GSK3α or GSK3β was observed,which was accompanied with increased phosphorylation of GSK3 substrates（e.g.CCAAT enhancer binding protein a,insulin receptor substrate 1,and TAU）,indicative of enhanced GSK3 activation.In addition,decreased protein mass of PI3K85α and tyrosinephosphorylation of PI3K50α was present in PBMC of the AMD patients,suggesting impaired PI3 K activation.Moreover,abnormally lowered molecular weight forms of Akt and GSK3 were detected in PBMC of the AMD patients.These data demonstrate that despite the presence of high levels of IL-17 RC,Wnt-3a and vascular endothelial growth factor,the PI3K/Akt/GSK3 signaling pathway is insensitive to these stimuli in PBMC of the AMD patients.Thus,measurement of PI3K/Akt/GSK3 expression and activity in PBMC may serve as a surrogate biomarker for AMD.展开更多
目的探讨红花多糖（safflower polysaccharide，sPs）体外对人外周血单个核细胞（PBMC）和CD8＋T细胞增殖作用的影响。方法采用葡聚糖-泛影葡胺密度梯度离心法（ficoll-hypaque density gradient centrifugation）从健康成人外周血中分...目的探讨红花多糖（safflower polysaccharide，sPs）体外对人外周血单个核细胞（PBMC）和CD8＋T细胞增殖作用的影响。方法采用葡聚糖-泛影葡胺密度梯度离心法（ficoll-hypaque density gradient centrifugation）从健康成人外周血中分离PBMC，在体外与不同浓度的SPS共同培养，用3H-TdR法检测PBMC增殖活性；流式细胞术检测CI）8＋T细胞的增殖情况。结果SPS能够促进PBMC增殖，尤其1．25g·L-1和0．625g·L-1。两组PBMC增殖作用明显，与对照组比较差异有统计学意义（P〈0．05）；SPS对CD8＋T细胞的增殖有促进作用，与对照组比较差异有统计学意义（P〈0．05）。结论SPS可促进PBMC、CD8＋T细胞的增殖，增强机体非特异性和特异性免疫功能。展开更多
基金supported by intramural research funding of National Center for Complementary and Alternative Medicine(now is National Center for Complementary and Integrative Health),NIH,the US Department of Health and Human Services(to X.L.)and an operating grant(MOP 123279)from Canadian Institutes for Health Research(to Z.Y.)
文摘Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C（IL-17RC）,a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration（AMD）,was associated with altered activation of phosphatidylinositide 3-kinase（PI3K）,Akt,and glycogen synthase kinase 3（GSK3）.We wondered whether or not altered PI3 K,Akt,and GSK3 activities could be detected in peripheral blood mononuclear cells（PBMC） obtained from AMD patients.In the patients＇ PBMC,absent or reduced serine-phosphorylation of GSK3α or GSK3β was observed,which was accompanied with increased phosphorylation of GSK3 substrates（e.g.CCAAT enhancer binding protein a,insulin receptor substrate 1,and TAU）,indicative of enhanced GSK3 activation.In addition,decreased protein mass of PI3K85α and tyrosinephosphorylation of PI3K50α was present in PBMC of the AMD patients,suggesting impaired PI3 K activation.Moreover,abnormally lowered molecular weight forms of Akt and GSK3 were detected in PBMC of the AMD patients.These data demonstrate that despite the presence of high levels of IL-17 RC,Wnt-3a and vascular endothelial growth factor,the PI3K/Akt/GSK3 signaling pathway is insensitive to these stimuli in PBMC of the AMD patients.Thus,measurement of PI3K/Akt/GSK3 expression and activity in PBMC may serve as a surrogate biomarker for AMD.
文摘目的探讨红花多糖（safflower polysaccharide，sPs）体外对人外周血单个核细胞（PBMC）和CD8＋T细胞增殖作用的影响。方法采用葡聚糖-泛影葡胺密度梯度离心法（ficoll-hypaque density gradient centrifugation）从健康成人外周血中分离PBMC，在体外与不同浓度的SPS共同培养，用3H-TdR法检测PBMC增殖活性；流式细胞术检测CI）8＋T细胞的增殖情况。结果SPS能够促进PBMC增殖，尤其1．25g·L-1和0．625g·L-1。两组PBMC增殖作用明显，与对照组比较差异有统计学意义（P〈0．05）；SPS对CD8＋T细胞的增殖有促进作用，与对照组比较差异有统计学意义（P〈0．05）。结论SPS可促进PBMC、CD8＋T细胞的增殖，增强机体非特异性和特异性免疫功能。
