Melittin has an Inhibitory Effect on TNF- -Induced Migration
of Human Aortic Smooth Muscle Cells by Blocking the MMP-9 Expression
Food Chem Toxicol, 2012 Aug 19
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-
-induced MMP-9 expression in the HASMCs. In addition, we found that the
inhibitory effects of melittin on TNF- -induced MMP-9 protein expression are
associated with the inhibition of MMP-9 transcription levels. Mechanistically,
Melittin suppressed TNF- -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- B via I B signaling
pathway. Moreover, the matrigel migration assay showed that melittin reduced
TNF- -induced HASMC migration.
These results suggest that melittin suppresses TNF- -induced
HASMC migration through the selective inhibition of MMP-9 expression and
provide a novel role of melittin in the anti-atherosclerotic action.
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