title: Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8.
abstract: 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.
authors.affiliation: New Experimental Therapeutics Branch, Division of Convergence Technology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Sung
authors.forename: Sooho
authors.initials: S
authors.lastname: Choi
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Chang Youp
authors.initials: CY
authors.lastname: Ok
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Weontae
authors.initials: W
authors.lastname: Lee
authors.forename: Kyun
authors.initials: K
authors.lastname: Heo
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D019906:Nuclear Magnetic Resonance, Biomolecular; D011869:Radioligand Assay
chemical_list: D052157:Aptamers, Nucleotide; D017931:DNA Primers; D016209:Interleukin-8
keywords: Aptamer; Interleukin-8 (IL-8); Neutrophil; Nuclear magnetic resonance (NMR); SELEX