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Nucleic acid-binding polymers as anti-inflammatory agents.

Publication ,  Journal Article
Lee, J; Sohn, JW; Zhang, Y; Leong, KW; Pisetsky, D; Sullenger, BA
Published in: Proc Natl Acad Sci U S A
August 23, 2011

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 23, 2011

Volume

108

Issue

34

Start / End Page

14055 / 14060

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • Shock, Septic
  • Polymers
  • Oligodeoxyribonucleotides
  • Nucleic Acids
  • Mice, Inbred C57BL
  • Mice
  • Liver Diseases
  • Ligands
  • Intracellular Space
 

Citation

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Lee, J., Sohn, J. W., Zhang, Y., Leong, K. W., Pisetsky, D., & Sullenger, B. A. (2011). Nucleic acid-binding polymers as anti-inflammatory agents. Proc Natl Acad Sci U S A, 108(34), 14055–14060. https://doi.org/10.1073/pnas.1105777108
Lee, Jaewoo, Jang Wook Sohn, Ying Zhang, Kam W. Leong, David Pisetsky, and Bruce A. Sullenger. “Nucleic acid-binding polymers as anti-inflammatory agents.Proc Natl Acad Sci U S A 108, no. 34 (August 23, 2011): 14055–60. https://doi.org/10.1073/pnas.1105777108.
Lee J, Sohn JW, Zhang Y, Leong KW, Pisetsky D, Sullenger BA. Nucleic acid-binding polymers as anti-inflammatory agents. Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14055–60.
Lee, Jaewoo, et al. “Nucleic acid-binding polymers as anti-inflammatory agents.Proc Natl Acad Sci U S A, vol. 108, no. 34, Aug. 2011, pp. 14055–60. Pubmed, doi:10.1073/pnas.1105777108.
Lee J, Sohn JW, Zhang Y, Leong KW, Pisetsky D, Sullenger BA. Nucleic acid-binding polymers as anti-inflammatory agents. Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14055–14060.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 23, 2011

Volume

108

Issue

34

Start / End Page

14055 / 14060

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • Shock, Septic
  • Polymers
  • Oligodeoxyribonucleotides
  • Nucleic Acids
  • Mice, Inbred C57BL
  • Mice
  • Liver Diseases
  • Ligands
  • Intracellular Space