Polypropylene glycol is a selective binding inhibitor for LTA and other structurally related TLR2 agonists
Polypropylene glycol is a selective binding inhibitor for LTA and other structurally related TLR2 agonists
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DOI：
10.1002/eji.200737466
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发表时间：
2008-03-01
影响因子：
5.4
通讯作者：
von Aulock, Sonja
中科院分区：
文献类型：
--
作者：
Draing, Christian;Traub, Stephanie;von Aulock, Sonja
聚丙二醇（PPG）通常被添加到细菌培养物中以避免起泡。然而，来自与PPG一起生长的细菌的脂磷壁酸（LTA）在人血液中缺乏对精氨酸的诱导效力。我们测试了几种二醇对人血液中葡萄球菌LTA的细胞因子应答的阻断效力。PPG 1200是检测的最有效的抑制剂，可诱导TNF、IL-1 β、IL-6、IL-8、IL-10和TGF-β，且无细胞毒性作用。PPG 1200也抑制金黄色葡萄球菌或Toll样受体（TLR）2激动剂（二酰化和三酰化脂肽和LTA）诱导的TNF诱导，但不抑制大肠杆菌或TLR 4激动剂诱导的TNF诱导。在流式细胞术研究中，携带PPG的纳米珠比具有甘油的纳米珠结合更多的罗丹明标记的LTA。此外，随着PPG 1200浓度的增加，孵育后LTA的H-1-NMR中的甲基峰发生位移。聚苯乙烯板与LTA，然后PPG 1200，然后血液的顺序孵育，中间有洗涤步骤，表明LTA诱导的TNF释放被抑制。但是，当PPG 1200与在加入LTA之前洗涤的血液一起预孵育时，TNF诱导没有受到抑制，表明PPG结合LTA而不是细胞结构。总之，PPG 1200是TLR 2激动剂诱导细胞因子的新型抑制剂，可直接干扰配体。
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-1 beta, 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 H-1-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.