title: 5'-nitro-indirubinoxime inhibits inflammatory response in TNF-alpha stimulated human umbilical vein endothelial cells.
abstract: Inflammation plays a critical role in the development of atherosclerosis and TNF-alpha, a major inflammatory cytokine, induces inflammatory responses by enhancing the expression of adhesion molecules and the secretion of inflammatory mediators. Indirubin is an active compound of Polygonum tinctorium Lour (P. tinctorium) that has the ability to suppress inflammation. Previously, we described the novel indirubin derivative, 5'-nitro-indirubinoxime (5'-NIO), and demonstrated that it has potent anti-proliferative activity against various human cancer cells. In this study, we examined the effect of 5'-NIO on the TNF-alpha induced inflammatory conditions of human umbilical vein endothelial cells (HUVECs). We found that 5'-NIO inhibited TNF-alpha induced MCP-1 and IL-8 expression at the RNA and protein levels in HUVECs. Specifically, 5'-NIO significantly inhibited the TNF-alpha stimulated release of MCP-1 and IL-8, with levels that were only 19.8% and 30.9% of those of untreated control cells, respectively. Furthermore, 5'-NIO largely inhibited the adhesion of U937 cells to HUVECs by decreasing the expression level of ICAM-1 and VCAM-1. Overall, these observations suggest that 5'-NIO has the potential for use as an anti-atherosclerotic agent.
authors.affiliation: Department of Biochemistry, Dongguk University College of Oriental Medicine, 707 Seokjang-dong, Gyeongju-si, Gyeongsangbuk-do 780-714, Gyeongju, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Won-Hwan
authors.initials: WH
authors.lastname: Park
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Ahn
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Si-Wouk
authors.initials: SW
authors.lastname: Kim
authors.forename: Soo-A
authors.initials: SA
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors*; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000037:antagonists & inhibitors*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: C534713:5'-nitroindirubinoxime; D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007211:Indoles; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010091:Oximes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D048031:JNK Mitogen-Activated Protein Kinases