The peptide lycosin-I attenuates TNF-α-induced inflammation in human umbilical vein endothelial cells via IκB/NF-κB signaling pathway.

Abstract

OBJECTIVE:

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.

MATERIALS AND METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Xianyao Li, Yaqin Tang, Binbin Ma, Zheng Wang, Jinying Jiang, Shengjie Hou, Shuhang Wang, Jie Zhang, Meichun Deng, Zhigui Duan, Xing Tang, Alex F Chen, Liping Jiang
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 67 Issue 5 Pg. 455-466 (May 2018) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 29523916 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antimicrobial Cationic Peptides
• Lipopolysaccharides
• NF-kappa B
• Spider Venoms
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• lycosin-I, Lycosa singorensis
• Intercellular Adhesion Molecule-1
• I-kappa B Kinase

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antimicrobial Cationic Peptides (pharmacology)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• I-kappa B Kinase (antagonists & inhibitors, biosynthesis)
• Inflammation (chemically induced, mortality, prevention & control)
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Lipopolysaccharides (antagonists & inhibitors)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors, biosynthesis)
• Signal Transduction (drug effects)
• Spider Venoms (pharmacology)
• Transcription Factor RelA (antagonists & inhibitors, biosynthesis)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)