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

Biomaterials. 2014 Jan;35(1):578-89. doi: 10.1016/j.biomaterials.2013.09.107. Epub 2013 Oct 13.

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.

Keywords: Aptamer; Interleukin-8 (IL-8); Neutrophil; Nuclear magnetic resonance (NMR); SELEX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • Base Sequence
  • DNA Primers
  • Humans
  • Interleukin-8 / chemistry
  • Interleukin-8 / pharmacology*
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Nuclear Magnetic Resonance, Biomolecular
  • Radioligand Assay

Substances

  • Aptamers, Nucleotide
  • DNA Primers
  • Interleukin-8