Polypropylene glycol is a selective binding inhibitor for LTA and other structurally related TLR2 agonists.
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-1beta, IL-6, IL-8, IL-10 and TGF-beta 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 (1)H-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.
Draing
Christian
C
Biochemical Pharmacology, University of Konstanz, Konstanz, Germany.
Traub
Stephanie
S
Deininger
Susanne
S
Mang
Philippa
P
Möller
Heiko M
HM
Manso
Miguel
M
Rossi
Francois
F
Morath
Siegfried
S
Hartung
Thomas
T
von Aulock
Sonja
S
D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D011409:Propylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology / Q000528:radiation effects; D013682:Teichoic Acids / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D014466:Ultraviolet Rays
D016207:Cytokines; D055666:Lipopeptides; D008070:Lipopolysaccharides; D009842:Oligopeptides; C508075:Pam(3)CSK(4) peptide; D010455:Peptides; D011108:Polymers; D011409:Propylene Glycols; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C012504:polypropylene glycol; D011092:Polyethylene Glycols; C009900:lipoteichoic acid; C106335:macrophage stimulatory lipopeptide 2