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Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8

机译:与白介素8结合的RNA适体对人嗜中性粒细胞活性的抑制

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摘要

Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis of several neutrophil-infiltrating chronic inflammatory diseases. In the current study, we generated and characterized a 2'-fluoro-pyrimidine modified RNA aptamer (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity and affinity, yielding an estimated KD of 1.72pM. NMR data revealed that the residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that can modulate multiple biological activities of IL-8 in human neutrophils, including migration, intracellular signaling, and intracellular Ca2+ mobilization. Our results suggest that the 8A-35 aptamer has great potential to be a lead structure in the development of effective therapeutic agents against inflammatory diseases.
机译:白介素8(IL-8)是一种促炎性CXC趋化因子,已与嗜中性粒细胞趋化性,脱粒作用以及几种嗜中性粒细胞浸润性慢性炎性疾病的发病机理有关。在当前的研究中,我们生成并表征了针对人IL-8的2'-氟-嘧啶修饰的RNA适体(8A-35)。 8A-35适体以高特异性和亲和力与IL-8结合,估计KD为1.72pM。 NMR数据显示IL-8的Lys8,Leu10,Val63,Val66,Lys69和Ala74的残基与适体相互作用。此外,8A-35适体具有有效的IL-8中和活性,可以调节人嗜中性白细胞中IL-8的多种生物学活性,包括迁移,细胞内信号传导和细胞内Ca2 +动员。我们的结果表明8A-35适体在开发有效的抗炎性疾病治疗剂方面具有巨大的潜力成为先导结构。

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