Centre for Human Drug Research, Leiden, The Netherlands.
Leiden Academic Center for Drug Research, Leiden, The Netherlands.
Clin Transl Sci. 2020 Sep;13(5):891-895. doi: 10.1111/cts.12789. Epub 2020 Apr 21.
LL-37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL-37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll-like receptors (TLRs). Omiganan pentahydrochloride is a synthetic cationic peptide in clinical development. Previously, omiganan was primarily known for its direct bactericidal and antifungal properties. We investigated whether omiganan enhances endosomal TLR responses, similar to LL-37. Human peripheral blood mononuclear cells were treated with endosomal TLR3, -7, -8, and -9 ligands in the presence of omiganan. Omiganan enhanced TLR-mediated interferon-α release. Subsequent experiments with TLR9 ligands showed that plasmacytoid dendritic cells were main contributors to omiganan-enhanced IFN production. Based on this type I interferon-enhancing effect, omiganan may qualify as potential treatment modality for virus-driven diseases. The molecular mechanism by which omiganan enhances endosomal TLR responses remains to be elucidated.
LL-37 是一种阳离子抗菌肽，也是唯一的人类 cathelicidins 家族成员。除了杀菌特性外，LL-37 还具有直接的免疫调节作用，其中包括通过内体 Toll 样受体 (TLR) 增强抗病毒反应。奥米加南五盐酸盐是一种正在临床开发中的合成阳离子肽。以前，奥米加南主要因其直接的杀菌和抗真菌特性而闻名。我们研究了奥米加南是否能增强内体 TLR 反应，类似于 LL-37。在奥米加南存在的情况下，用内体 TLR3、-7、-8 和 -9 配体处理人外周血单核细胞。奥米加南增强了 TLR 介导的干扰素-α释放。随后用 TLR9 配体进行的实验表明，浆细胞样树突状细胞是奥米加南增强 IFN 产生的主要贡献者。基于这种 I 型干扰素增强作用，奥米加南可能有资格成为病毒驱动疾病的潜在治疗方法。奥米加南增强内体 TLR 反应的分子机制仍有待阐明。
