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Updated: May 19, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Melittin has an inhibitory effect on TNF-α-induced migration of human aortic smooth muscle cells by blocking the
Yun-Jeong Jeong1, Hyun-Ji Cho, Key Whang
1Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
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.
Insights
Melittin, a bee venom component, inhibits matrix metalloproteinases-9 (MMP-9) and vascular smooth muscle cell migration. This suggests melittin
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pharmacology
Background:
- Matrix metalloproteinases-9 (MMP-9) is implicated in atherosclerosis and vascular smooth muscle cell (VSMC) migration.
- Understanding the molecular mechanisms of anti-atherosclerotic compounds is crucial.
Purpose of the Study:
- To investigate the anti-atherosclerotic effects of melittin in human aortic smooth muscle cells (HASMCs).
- To elucidate the molecular mechanisms by which melittin impacts MMP-9 expression and VSMC migration.
Main Methods:
- Assessed MMP-9 and MMP-2 secretion and TNF-α-induced MMP-9 expression in HASMCs.
- Analyzed MMP-9 transcription levels and activity.
- Investigated the effects of melittin on p38, ERK1/2, JNK, and Akt phosphorylation.
- Utilized reporter gene assays, western blotting, and matrigel migration assays.
Main Results:
- Melittin significantly suppressed MMP-9 and MMP-2 secretion.
- Melittin inhibited TNF-α-induced MMP-9 expression and transcription.
- Melittin blocked TNF-α-induced MMP-9 activity by inhibiting p38 and ERK1/2 phosphorylation.
- Melittin suppressed NF-κB activation via the IκBα signaling pathway.
- Melittin reduced TNF-α-induced HASMC migration.
Conclusions:
- Melittin exhibits anti-atherosclerotic properties by inhibiting HASMC migration.
- Melittin's mechanism involves the selective suppression of MMP-9 expression and activity.
- Melittin represents a potential therapeutic agent for atherosclerosis.
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