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 journalArticlepeer-review

    70 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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