Nucleic acid-binding polymers as anti-inflammatory agents.

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.

authors

Lee J,Sohn JW,Zhang Y,Leong KW,Pisetsky D,Sullenger BA

doi

10.1073/pnas.1105777108

subject

Has Abstract

pub_date

2011-08-23 00:00:00

pages

14055-60

issue

34

eissn

0027-8424

issn

1091-6490

pii

1105777108

journal_volume

108

pub_type

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