CpG-c41分子對TLR7-MyD88依賴型信號通路的交叉干擾作用
發(fā)布時間:2018-05-25 02:25
本文選題:CpG-c + ssRNA ; 參考:《第三軍醫(yī)大學(xué)學(xué)報》2013年10期
【摘要】:目的探討TLR9強力拮抗劑CpG-c41分子對TLR7-MyD88依賴型信號通路的交叉干擾作用。方法體外實驗采用ELISA法檢測CpG-c41對TLR7激動劑ssRNA83刺激RAW264.7細(xì)胞24 h誘發(fā)的炎癥介質(zhì)TNF-α和IL-6表達(dá)的影響,Western blot檢測CpG-c41對TLR7-MyD88依賴型信號通路中IκBα蛋白表達(dá)的影響;體內(nèi)實驗采用ELISA法檢測CpG-c41對ssRNA83攻擊BALB/c小鼠2 h誘發(fā)血清中TNF-α和IL-6表達(dá)的影響作用。結(jié)果體內(nèi)、體外實驗均表明,CpG-c41分子能夠顯著抑制經(jīng)ssRNA83刺激誘發(fā)TLR7-MyD88依賴型信號通路介導(dǎo)的炎癥介質(zhì)TNF-α和IL-6的釋放(P0.01),體外實驗表明抑制作用具有量效關(guān)系;而Western blot檢測顯示在CpG-c41作用下,TLR7-MyD88依賴型信號通路中IκBα的降解受干擾。結(jié)論 TLR9強力拮抗劑CpG-c41分子通過干擾TLR7-MyD88依賴型信號通路中IκBα的磷酸化降解,抑制炎癥介質(zhì)的釋放,發(fā)揮對ssRNA攻擊小鼠的免疫保護(hù)作用。
[Abstract]:Objective to investigate the cross-interference of CpG-c41 molecule, a strong TLR9 antagonist, on the TLR7-MyD88 dependent signaling pathway. Methods the effect of CpG-c41 on the expression of TNF- 偽 and IL-6 in RAW264.7 cells stimulated by TLR7 agonist ssRNA83 for 24 h was detected by ELISA assay. The effect of CpG-c41 on the expression of I 魏 B 偽 protein in TLR7-MyD88 dependent signaling pathway was detected by Western blot. The effect of CpG-c41 on the expression of TNF- 偽 and IL-6 in serum of BALB/c mice induced by ssRNA83 for 2 h was detected by ELISA method in vivo. Results both in vivo and in vitro experiments showed that CpG-c41 could significantly inhibit the release of TNF- 偽 and IL-6 mediated by TLR7-MyD88 dependent signaling pathway induced by ssRNA83. In vitro, the inhibitory effect was dose-dependent. Western blot detection showed that the degradation of I 魏 B 偽 in TLR7-MyD88 dependent signaling pathway was interfered with by CpG-c41. Conclusion CpG-c41, a powerful TLR9 antagonist, inhibits the release of inflammatory mediators by interfering with the phosphorylation and degradation of I 魏 B 偽 in the TLR7-MyD88 dependent signaling pathway, thus exerting an immune protective effect on mice attacked by ssRNA.
【作者單位】: 第三軍醫(yī)大學(xué)西南醫(yī)院綜合實驗研究中心;
【基金】:重慶市自然科學(xué)基金(CSTC2013jjb0128)~~
【分類號】:R329-33
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