Xianyao Li1, Yaqin Tang1, Binbin Ma1, Zheng Wang2, Jinying Jiang3, Shengjie Hou1, Shuhang Wang1, Jie Zhang1, Meichun Deng4, Zhigui Duan5, Xing Tang6, Alex F Chen7,8, Liping Jiang9,10. 1. Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China. 2. The First Department of General Surgery, the Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China. 3. Department of Neonatology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan, China. 4. Department of Biochemistry, School of Life Sciences, Central South University, Changsha, 410013, Hunan, China. 5. Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China. 6. College of Chemistry, Biology, and Material Science, East China Institute of Technology, Nanchang, 330013, Jiangxi, China. 7. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, Hunan, China. afychen@yahoo.com. 8. Center for Vascular Disease and Translational Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China. afychen@yahoo.com. 9. Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China. jiangliping@csu.edu.cn. 10. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, Hunan, China. jiangliping@csu.edu.cn.
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.
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: Simone de Haij; Astrid C Bakker; Reinier N van der Geest; Guy Haegeman; Wim Vanden Berghe; Jamil Aarbiou; Mohamed R Daha; Cees van Kooten Journal: J Am Soc Nephrol Date: 2005-04-20 Impact factor: 10.121