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首页> 外文期刊>Inflammation >A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-α
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A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-α

机译:人TNF受体1 CRD4的A1模块衍生的合成肽抑制人TNF-α的结合和促炎作用

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摘要

Tumour necrosis factor α (TNF-α) is a proinflammatory cytokine, which has been shown to be a causative factor in rheumatoid arthritis, inflammatory bowel disease and septic shock. Proinflammatory effect of TNF-α is activated mainly through human TNF receptor-1 (TNF-R1). However, the role of the fourth cystein-rich domain (CRD4) of TNF-R1 extracellular portion in the interaction of TNF-α with TNF-R1 is still unclear. In the present study, binding activity of TNF-α to TNF-R1 and protein levels of IκB-α and nuclear transcription factor kappa B (NF-κB) p65 subunit in HeLa cells were measured using enzyme-linked immunosorbent assay (ELISA) and western-blot analysis. Pep 3 (LRENECVS) which was derived from the hydrophilic region of A1 module in CRD4 remarkably inhibited the binding of TNF-α to TNF-R1, and also reversed TNF-α-induced degradation of IκB-α and nuclear translocation of NF-κB p65 subunit in HeLa cells. Our results confirmed that the hydrophilic region of A1 module in CRD4 participated in the interaction of TNF-α with TNF-R1, and demonstrated the potential of small-molecule TNF-α extracellular inhibitors targeting at A1 module in CRD4 of TNF-R1 in suppressing proinflammatory effect of TNF-α.
机译:肿瘤坏死因子α(TNF-α)是促炎细胞因子,已被证明是类风湿关节炎,炎症性肠病和败血性休克的病因。 TNF-α的促炎作用主要通过人TNF受体1(TNF-R1)激活。但是,尚不清楚TNF-R1细胞外部分的第四个富半胱氨酸结构域(CRD4)在TNF-α与TNF-R1相互作用中的作用。在本研究中,使用酶联免疫吸附测定(ELISA)和ELISA检测HeLa细胞中TNF-α与TNF-R1的结合活性以及IκB-α和核转录因子kappa B(NF-κB)p65亚基的蛋白水平。蛋白质印迹分析。来自CRD4中A1组件亲水区的Pep 3(LRENECVS)显着抑制TNF-α与TNF-R1的结合,并逆转TNF-α诱导的IκB-α降解和NF-κB核转运HeLa细胞中的p65亚基。我们的结果证实,CRD4中A1模块的亲水区域参与了TNF-α与TNF-R1的相互作用,并证明了针对TNF-R1 CRD4中A1模块的小分子TNF-α细胞外抑制剂的抑制作用TNF-α的促炎作用。

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