Polypropylene glycol is a selective binding inhibitor for LTA and other structurally related TLR2 agonists

Christian Draing, Stephanie Traub, Susanne Deininger, Philippa Mang, Heiko M. Möller, Miguel Manso, Francois Rossi, Siegfried Morath, Thomas Hartung, Sonja von Aulock

Research output: Contribution to journalArticlepeer-review

Abstract

Polypropylene glycol (PPG) is commonly added to bacterial cultures to avoid foaming. However, lipoteichoic acid (LTA) from bacteria grown with PPG lacked cytokine-inducing potency in human blood. We tested the blocking efficacy of several glycols on the cytokine response to staphylococcal LTA in human blood. PPG 1200 was the most potent inhibitor tested, shown for TNF, IL-1β, IL-6, IL-8, IL-10 and TGF-β induction, and displayed no cytotoxic effects. TNF induction by Staphylococcus aureus or by Toll-like receptor (TLR)2 agonists (di- and triacylated lipopeptides and LTA) was also inhibited by PPG 1200, but not that induced by Escherichia coli or TLR4 agonists. In flow cytometric studies, PPG-carrying nanobeads bound more rhodamine-labeled LTA than those with glycerol. Additionally, the methyl group peak in the 1H-NMR of LTA shifted after incubation with increasing PPG 1200 concentrations. Sequential incubation of polystyrene plates with LTA, then PPG 1200 and then blood, with washing steps in between, showed that LTA-induced TNF release was inhibited. But when PPG 1200 was pre-incubated with blood that was washed before LTA was added, TNF induction was not repressed, demonstrating that PPG binds LTA and not cellular structures. In summary, PPG 1200 is a novel inhibitor of cytokine induction by TLR2 agonists, which interferes directly with the ligands.

Original languageEnglish (US)
Pages (from-to)797-808
Number of pages12
JournalEuropean Journal of Immunology
Volume38
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

Keywords

  • Innate immunity
  • Lipoteichoic acid
  • Polypropylene glycol
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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