Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
The First Department of General Surgery, the Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Inflamm Res. 2018 May;67(5):455-466. doi: 10.1007/s00011-018-1138-7. Epub 2018 Mar 10.
The peptide lycosin-I has anti-bacterial and anti-cancer capacities. However, the anti-inflammatory activity of lycosin-I remains unknown. We investigated whether lycosin-I could attenuate inflammation.
Human umbilical vein endothelial cells (HUVECs) were treated with lycosin-I before exposure to tumor necrosis factor-α (TNF-α). The expression of intercellular cell adhesion molecule-1 (ICAM-1), nuclear transcription factor-kappa B (NF-κB) p65 and inhibitory subunit of NF-κB alpha (IκBα) was evaluated by western blot. The expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) was detected by quantitative RT-PCR or ELISA. Immunofluorescence analysis was used to determine the impact of lycosin-I on NF-κB pathway. C57BL/6 mice were pretreated with lycosin-I before exposure with lipopolysaccharide (LPS).
Lycosin-I significantly reduced the TNF-α-enhanced expression of IL-6, IL-8 and ICAM-1. Lycosin-I also inhibited the human monocyte cells adhesion to HUVECs. We further demonstrated that lycosin-I could effectively suppress the reaction of endothelial cells to TNF-α by inhibiting IκBα degradation. Subsequently, the phosphorylation and translocation of NF-κB p65 could also be attenuated. Furthermore, lycosin-I exhibited a significant protection of C57BL/6 mice against LPS-induced death.
Our results suggested that the anti-inflammatory activity of lycosin-I was associated with NF-κB activation and lycosin-I had potential to be a novel therapeutic candidate for inflammatory diseases.
肽聚糖 Lycosin-I 具有抗菌和抗癌能力。然而，Lycosin-I 的抗炎活性尚不清楚。我们研究了 Lycosin-I 是否可以减轻炎症。
人脐静脉内皮细胞 (HUVEC) 在暴露于肿瘤坏死因子-α (TNF-α) 之前用 Lycosin-I 处理。通过 Western blot 评估细胞间黏附分子-1 (ICAM-1)、核转录因子-κB (NF-κB) p65 和 NF-κB 抑制亚基α (IκBα) 的表达。通过定量 RT-PCR 或 ELISA 检测白细胞介素-6 (IL-6) 和白细胞介素-8 (IL-8) 的表达。免疫荧光分析用于确定 Lycosin-I 对 NF-κB 途径的影响。C57BL/6 小鼠在用脂多糖 (LPS) 暴露前用 Lycosin-I 预处理。
Lycosin-I 显著降低了 TNF-α 增强的 IL-6、IL-8 和 ICAM-1 的表达。Lycosin-I 还抑制了人单核细胞与 HUVECs 的黏附。我们进一步证明，Lycosin-I 通过抑制 IκBα 降解，有效地抑制内皮细胞对 TNF-α 的反应。随后，NF-κB p65 的磷酸化和易位也可以被抑制。此外，Lycosin-I 对 C57BL/6 小鼠对 LPS 诱导的死亡具有显著的保护作用。
我们的结果表明，Lycosin-I 的抗炎活性与 NF-κB 激活有关，Lycosin-I 有可能成为炎症性疾病的新型治疗候选药物。
