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

Ho Jin Sung, Sooho Choi, Ji Won Lee, Chang Youp Ok, Yoe Sik Bae, Yun Hee Kim, Weontae Lee, Kyun Heo, In Hoo Kim

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)578-589
Number of pages12
JournalBiomaterials
Volume35
Issue number1
DOIs
Publication statusPublished - 2014

Bibliographical note

Funding Information:
This work was supported by research grants from the National Cancer Center Grant ( NCC1210330 ).

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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