Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8.
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 Ca(2+) 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.
['Sung|Ho Jin|HJ|', 'Choi|Sooho|S|', 'Lee|Ji Won|JW|', 'Ok|Chang Youp|CY|', 'Bae|Yoe-Sik|YS|', 'Kim|Yun-Hee|YH|', 'Lee|Weontae|W|', 'Heo|Kyun|K|', 'Kim|In-Hoo|IH|']
D052157:Aptamers, Nucleotide D001483:Base Sequence D017931:DNA Primers D006801:Humans D016209:Interleukin-8 D009504:Neutrophils D019906:Nuclear Magnetic Resonance, Biomolecular D011869:Radioligand Assay
Neutrophil Aptamer Interleukin-8 (IL-8) Nuclear magnetic resonance (NMR) SELEX