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

被引：39

作者：

Sung, Ho Jin ^{[1
]}

Choi, Sooho ^{[2
]}

Lee, Ji Won ^{[1
]}

Ok, Chang Youp ^{[3
]}

Bae, Yoe-Sik ^{[3
]}

Kim, Yun-Hee ^{[4
]}

Lee, Weontae ^{[2
]}

Heo, Kyun ^{[1
]}

Kim, In-Hoo ^{[4
]}

机构：

[1] Natl Canc Ctr, Div Convergence Technol, New Expt Therapeut Branch, Goyang Si 410769, Gyeonggi Do, South Korea

[2] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 120749, South Korea

[3] Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea

[4] Natl Canc Ctr, Div Convergence Technol, Mol Imaging & Therapy Branch, Goyang Si 410769, Gyeonggi Do, South Korea

来源：

BIOMATERIALS | 2014年 / 35卷 / 01期

关键词：

Aptamer; SELEX; Interleukin-8 (IL-8); Nuclear magnetic resonance (NMR); Neutrophil; EXPRESSION REGULATES TUMORIGENICITY; CANCER CELLS; TUMOR-CELLS; IN-VITRO; METASTASIS; CARCINOMA; THERAPEUTICS; ANGIOGENESIS; RESISTANCE; CHEMOKINE;

D O I：

10.1016/j.biomaterials.2013.09.107

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

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 K-D of 1.72 pM. 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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：578 / 589

页数：12

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