This study examines the effect of co-administration of antimicrobial peptides and the synthetic glycolipid FP7, which is active in inhibiting inflammatory cytokine production caused by TLR4 activation and signaling. The co-administration of two lipopolysaccharide (LPS)-neutralizing peptides (a cecropin A-melittin hybrid peptide and a human cathelicidin) enhances by an order of magnitude the potency of FP7 in blocking the TLR4 signal. Interestingly, this is not an additional effect of LPS neutralization by peptides, because it also occurs if cells are stimulated by the plant lectin phytohemagglutinin, a non-LPS TLR4 agonist. Our data suggest a dual mechanism of action for the peptides, not exclusively based on LPS binding and neutralization, but also on a direct effect on the LPS-binding proteins of the TLR4 receptor complex. NMR experiments in solution show that peptide addition changes the aggregation state of FP7, promoting the formation of larger micelles. These results suggest a relationship between the aggregation state of lipid A-like ligands and the type and intensity of the TLR4 response.

中文翻译：

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共同施用抗菌肽可增强合成糖脂的Toll样受体4拮抗剂活性。

这项研究检查了抗菌肽和合成糖脂FP7共同给药的作用，后者可抑制由TLR4激活和信号转导引起的炎症细胞因子的产生。两种中性脂多糖（LPS）中和肽（天蚕素A-melittin杂合肽和人cathelicidin）的共同给药可提高FP7阻断TLR4信号的能力。有趣的是，这不是肽对LPS的中和作用，因为如果细胞被植物凝集素植物血凝素（一种非LPS TLR4激动剂）刺激，也会发生这种作用。我们的数据表明该肽的双重作用机制，不仅是基于LPS结合和中和，而且还直接作用于TLR4受体复合物的LPS结合蛋白。溶液中的NMR实验表明，肽的添加改变了FP7的聚集状态，从而促进了较大胶束的形成。这些结果表明脂质A样配体的聚集状态与TLR4反应的类型和强度之间的关系。