Toll样受体2对人主动脉瓣间质细胞炎症反应的调控作用
发布时间：2018-09-05 09:33
【摘要】：目的探讨Toll样受体(TLR2)调控Notch1信号通路对人主动脉瓣间质细胞炎症反应的作用。方法从正常主动脉瓣组织及主动脉瓣狭窄病人的主动脉瓣组织中分离出主动脉瓣间质细胞,酶联免疫吸附(ELISA)检测200 ng/ml的TLR2激活物脂多糖(LPS)干预细胞24 h后白细胞介素(IL)-6、巨细胞趋化因子(MCP)-1和细胞间黏附因子(ICAM)-1浓度;Western印迹检测200 ng/ml的LPS干预细胞2、4、8、12 h后NICD1蛋白表达,ELISA检测Jagged1浓度;60 nmol/L的人Notch1特异性siRNA沉默Notch1及200 ng/ml的LPS刺激细胞24 h后,Western印迹检测NICD1及ICAM-1蛋白表达;5μg/ml的Jagged1及200 ng/ml的LPS处理细胞,ELISA检测IL-6、MCP-1和ICAM-1浓度。结果正常主动脉瓣组织及主动脉狭窄病人瓣膜组织的主动脉瓣间质细胞经LPS刺激后IL-6、MCP-1和VCAM-1的浓度均显著高于无LPS刺激组,主动脉狭窄病人瓣膜组织的主动脉瓣间质细胞中IL-6、MCP-1和VCAM-1的浓度均显著高于正常组(P0.01);LPS刺激能诱导NICD1的生成及增加,具有时间依赖性,且主动脉狭窄病人瓣膜组织的主动脉瓣膜间质细胞中NICD1生成量多于正常组;主动脉狭窄病人瓣膜组织的主动脉瓣膜间质细胞中Jagged1浓度显著高于正常组,且随着时间延长增加;沉默Notch1信号通路能减弱NICD1的蛋白表达,且能减少炎症因子ICAM-1的蛋白表达;Jagged1激活Notch信号通路能诱导产生低水平的IL-6、MCP-1、ICAM-1,而能明显增强TLR2诱导的IL-6、MCP-1、ICAM-1的水平。结论 TLR2能诱导人主动脉瓣间质细胞的炎症反应及活化Notch1信号通路,主动脉瓣狭窄的主动脉瓣组织间质细胞炎症反应更明显,沉默Notch1信号通路可减弱TLR2诱导的炎症反应,激活Notch信号通路则增强TLR2诱导的炎症反应。
[Abstract]:Objective To investigate the effect of Toll-like receptor (TLR2) on the inflammatory response of human aortic valve interstitial cells (ASCs) mediated by Notch1 signaling pathway. Interleukin-6 (IL-6), giant cell chemokine (MCP-1) and intercellular adhesion factor (ICAM-1) concentrations were measured 24 hours after preconditioning; NICD1 protein expression was detected by Western blot after L PS intervention of 200 ng/ml for 2,4,8,12 hours; Jagged1 concentration was detected by ELISA; Notch1-specific siRNA silenced Notch1 and 200 ng/ml L PS-stimulated cells 24 hours after Western blotting. The expressions of NICD1 and ICAM-1 were detected by Western blot, and the concentrations of IL-6, MCP-1 and ICAM-1 were detected by ELISA in 5 ug/ml Jagged 1 and 200 ng/ml LPS treated cells. The concentrations of IL-6, MCP-1 and VCAM-1 in the valvular stromal cells of patients with aortic stenosis were significantly higher than those of normal control group (P 0.01); LPS stimulation could induce the production and increase of NICD1 in a time-dependent manner, and the production of NICD1 in the valvular stromal cells of patients with aortic stenosis was more than that of normal control group. The concentration of Jagged 1 in human aortic valve stromal cells was significantly higher than that in normal control group, and increased with time; silencing Notch 1 signaling pathway decreased the expression of NICD 1 protein and the expression of inflammatory factor ICAM-1; activating Notch signaling pathway by Jagged 1 could induce the production of low levels of IL-6, MCP-1, ICAM-1, but could significantly reduce the expression of inflammatory factor ICAM-1. Conclusion TLR2 can induce inflammation and activate Notch 1 signaling pathway in human aortic valve stromal cells, especially in aortic valve stenosis. Silence of Notch 1 signaling pathway can attenuate TLR2-induced inflammation and increase Notch signaling pathway. Strong TLR2 induced inflammatory response.
【作者单位】： 兰州大学第二医院心内科;咸阳市第一人民医院心内科;
【分类号】：R542.5
[Abstract]:Objective To investigate the effect of Toll-like receptor (TLR2) on the inflammatory response of human aortic valve interstitial cells (ASCs) mediated by Notch1 signaling pathway. Interleukin-6 (IL-6), giant cell chemokine (MCP-1) and intercellular adhesion factor (ICAM-1) concentrations were measured 24 hours after preconditioning; NICD1 protein expression was detected by Western blot after L PS intervention of 200 ng/ml for 2,4,8,12 hours; Jagged1 concentration was detected by ELISA; Notch1-specific siRNA silenced Notch1 and 200 ng/ml L PS-stimulated cells 24 hours after Western blotting. The expressions of NICD1 and ICAM-1 were detected by Western blot, and the concentrations of IL-6, MCP-1 and ICAM-1 were detected by ELISA in 5 ug/ml Jagged 1 and 200 ng/ml LPS treated cells. The concentrations of IL-6, MCP-1 and VCAM-1 in the valvular stromal cells of patients with aortic stenosis were significantly higher than those of normal control group (P 0.01); LPS stimulation could induce the production and increase of NICD1 in a time-dependent manner, and the production of NICD1 in the valvular stromal cells of patients with aortic stenosis was more than that of normal control group. The concentration of Jagged 1 in human aortic valve stromal cells was significantly higher than that in normal control group, and increased with time; silencing Notch 1 signaling pathway decreased the expression of NICD 1 protein and the expression of inflammatory factor ICAM-1; activating Notch signaling pathway by Jagged 1 could induce the production of low levels of IL-6, MCP-1, ICAM-1, but could significantly reduce the expression of inflammatory factor ICAM-1. Conclusion TLR2 can induce inflammation and activate Notch 1 signaling pathway in human aortic valve stromal cells, especially in aortic valve stenosis. Silence of Notch 1 signaling pathway can attenuate TLR2-induced inflammation and increase Notch signaling pathway. Strong TLR2 induced inflammatory response.
【作者单位】： 兰州大学第二医院心内科;咸阳市第一人民医院心内科;
【分类号】：R542.5
【相似文献】
相关期刊论文 前1条
1 李慧媛;张冬雷;张岘;付荣凤;宣e，
本文编号：2223879
本文链接：https://www.wllwen.com/yixuelunwen/xxg/2223879.html
最近更新
教材专著
