Nucleic acid-binding polymers as anti-inflammatory agents

Jaewoo Lee, Jang Wook Sohn, Ying Zhang, Kam W. Leong, David Pisetsky, Bruce A. Sullenger

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids.

Original languageEnglish
Pages (from-to)14055-14060
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number34
DOIs
Publication statusPublished - 2011 Aug 23

Keywords

  • Damage-associated molecular pattern
  • Inflammation
  • Pattern-recognition receptor

ASJC Scopus subject areas

  • General

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