Melittin has an inhibitory effect on TNF-alpha-induced migration of human aortic smooth muscle cells by blocking the MMP-9 expression

作者：Jeong Yun Jeong; Cho Hyun Ji; Whang Key; Lee In Seon; Park Kwan Kyu; Choe Jung Yoon; Han Sang Mi; Kim Cheorl Ho; Chang Hyeun Wook; Moon Sung Kwon; Kim Wun Jae; Choi Yung Hyun; Chang Young Chae^*

来源：Food and Chemical Toxicology, 2012, 50(11): 3996-4002.

DOI：10.1016/j.fct.2012.08.026

• Atherosclerosis
• Melittin
• Bee venom
• VSMC

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-alpha-induced MMP-9 expression in the HASMCs. In addition, we found that the inhibitory effects of melittin. on TNF-alpha-induced MMP-9 protein expression are associated with the inhibition of MMP-9 transcription levels. Mechanistically, Melittin suppressed TNF-alpha-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-kappa B via I kappa B alpha signaling pathway. Moreover, the matrigel migration assay showed that melittin reduced TNF-alpha-induced HASMC migration. These results suggest that melittin suppresses TNF-alpha-induced HASMC migration through the selective inhibition of MMP-9 expression and provide a novel role of melittin in the anti-atherosclerotic action.

• 出版日期2012-11