Toll樣受體2對人主動脈瓣間質(zhì)細胞炎癥反應(yīng)的調(diào)控作用
發(fā)布時間：2018-09-05 09:33
【摘要】：目的探討Toll樣受體(TLR2)調(diào)控Notch1信號通路對人主動脈瓣間質(zhì)細胞炎癥反應(yīng)的作用。方法從正常主動脈瓣組織及主動脈瓣狹窄病人的主動脈瓣組織中分離出主動脈瓣間質(zhì)細胞,酶聯(lián)免疫吸附(ELISA)檢測200 ng/ml的TLR2激活物脂多糖(LPS)干預(yù)細胞24 h后白細胞介素(IL)-6、巨細胞趨化因子(MCP)-1和細胞間黏附因子(ICAM)-1濃度;Western印跡檢測200 ng/ml的LPS干預(yù)細胞2、4、8、12 h后NICD1蛋白表達,ELISA檢測Jagged1濃度;60 nmol/L的人Notch1特異性siRNA沉默Notch1及200 ng/ml的LPS刺激細胞24 h后,Western印跡檢測NICD1及ICAM-1蛋白表達;5μg/ml的Jagged1及200 ng/ml的LPS處理細胞,ELISA檢測IL-6、MCP-1和ICAM-1濃度。結(jié)果正常主動脈瓣組織及主動脈狹窄病人瓣膜組織的主動脈瓣間質(zhì)細胞經(jīng)LPS刺激后IL-6、MCP-1和VCAM-1的濃度均顯著高于無LPS刺激組,主動脈狹窄病人瓣膜組織的主動脈瓣間質(zhì)細胞中IL-6、MCP-1和VCAM-1的濃度均顯著高于正常組(P0.01);LPS刺激能誘導(dǎo)NICD1的生成及增加,具有時間依賴性,且主動脈狹窄病人瓣膜組織的主動脈瓣膜間質(zhì)細胞中NICD1生成量多于正常組;主動脈狹窄病人瓣膜組織的主動脈瓣膜間質(zhì)細胞中Jagged1濃度顯著高于正常組,且隨著時間延長增加;沉默Notch1信號通路能減弱NICD1的蛋白表達,且能減少炎癥因子ICAM-1的蛋白表達;Jagged1激活Notch信號通路能誘導(dǎo)產(chǎn)生低水平的IL-6、MCP-1、ICAM-1,而能明顯增強TLR2誘導(dǎo)的IL-6、MCP-1、ICAM-1的水平。結(jié)論 TLR2能誘導(dǎo)人主動脈瓣間質(zhì)細胞的炎癥反應(yīng)及活化Notch1信號通路,主動脈瓣狹窄的主動脈瓣組織間質(zhì)細胞炎癥反應(yīng)更明顯,沉默Notch1信號通路可減弱TLR2誘導(dǎo)的炎癥反應(yīng),激活Notch信號通路則增強TLR2誘導(dǎo)的炎癥反應(yīng)。
[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.
【作者單位】： 蘭州大學(xué)第二醫(yī)院心內(nèi)科;咸陽市第一人民醫(yī)院心內(nèi)科;
【分類號】：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.
【作者單位】： 蘭州大學(xué)第二醫(yī)院心內(nèi)科;咸陽市第一人民醫(yī)院心內(nèi)科;
【分類號】：R542.5
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