title: Melittin has an inhibitory effect on TNF-α-induced migration of human aortic smooth muscle cells by blocking the MMP-9 expression.
abstract: Matrix metalloproteinases-9 (MMP-9) plays an important role in the pathogenesis of atherosclerosis and migration of vascular smooth muscle cells (VSMCs) after an arterial injury. In this study, we investigated the potential molecular mechanisms underlying the anti-atheroscleroic effects of melittin, a major component of bee venom, in human aortic smooth muscle cells (HASMCs). Melttin significantly suppressed MMP-9 and MMP-2 secretion, as well as TNF-α-induced MMP-9 expression in the HASMCs. In addition, we found that the inhibitory effects of melittin on TNF-α-induced MMP-9 protein expression are associated with the inhibition of MMP-9 transcription levels. Mechanistically, Melittin suppressed TNF-α-induced MMP-9 activity by inhibiting the phosphorylation of p38 and ERK1/2, but did not affect the phosphorylation of JNK and Akt. Reporter gene and western blotting assays showed that melittin inhibits MMP-9 transcriptional activity by blocking the activation of NF-κB via IκBα signaling pathway. Moreover, the matrigel migration assay showed that melittin reduced TNF-α-induced HASMC migration. These results suggest that melittin suppresses TNF-α-induced HASMC migration through the selective inhibition of MMP-9 expression and provide a novel role of melittin in the anti-atherosclerotic action.
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Cho
authors.forename: Key
authors.initials: K
authors.lastname: Whang
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Lee
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Hyeun-Wook
authors.initials: HW
authors.lastname: Chang
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D008555:Melitten / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D008555:Melitten; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9