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

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

doi:10.1016/j.fct.2012.08.026

Cited by 25 publications

(15 citation statements)

References 37 publications

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“…The total length of the structural gene is 27 kb, which differs from other MMPs due to the MMP-2 gene 5′ flanking sequence that contains two GC boxes instead of two TATA sequences, which promotes the subregion (19). MMP-2 can decompose the stromal component among the cells and type IV collagen, which is the main component of the basement membrane (20–22). Previous studies have reported that the expression of MMP-2 increases during early AS pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Xin Mai Jia ultrafiltration extract on human umbilical vein endothelial cell injury induced by hydrogen peroxide and the effect on the NO-cGMP signaling pathway

Yin

Wan

et al. 2014

Experimental and Therapeutic Medicine

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The aim of the present study was to evaluate the protective effect of the ultrafiltration extract of Xin Mai Jia (XMJ) on a human umbilical vein endothelial cell (HUVEC) injury model induced by hydrogen peroxide (H2O2), by providing experimental data to investigate the mechanism and efficacy underlying the therapeutic effects on atherosclerosis. HUVECs were first injured by H2O2 and then varying final concentrations of the Chinese herb extract were added. Effects of the XMJ extract on morphology, activity, monolayer permeability, biochemical indicators, cytokines, endothelial nitric oxide synthase (eNOS) protein content and eNOS gene expression in the HUVECs were analyzed. H2O2 significantly promoted HUVEC injury. The XMJ ultrafiltration extract significantly improved the morphological changes in the injured HUVECs. In addition, XMJ treatment increased cell activity and decreased monolayer permeability. The expression levels of intracellular adhesion molecule-1, vascular adhesion molecule-1, interleukin-1 and -6 and nuclear factor-κB decreased, while the expression levels of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 increased with XMJ administration. Increased levels of nitric oxide (NO), eNOS protein and eNOS gene expression were also observed. Therefore, the XMJ ultrafiltration extract exhibits marked anti-inflammatory effects and antioxidant abilities. These properties significantly inhibited the H2O2-induced injury of HUVECs, which may be associated with the NO-cyclic guanosine monophosphate signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Protective effect of Xin Mai Jia ultrafiltration extract on human umbilical vein endothelial cell injury induced by hydrogen peroxide and the effect on the NO-cGMP signaling pathway

Yin

Wan

et al. 2014

Experimental and Therapeutic Medicine

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“…Melittin has been proposed as a possible anticancer drugs with high potential and the antibacterial, antiviral, anti-inflammatory and anticancer properties demonstrated by the protein have been previously described (1)(2)(3)(4). Numerous studies have reported several mechanisms of melittin cytotoxicity in various types of cancer cells, with mechanisms including growth inhibition, induction of apoptosis, cell cycle alterations and an effect on proliferation (5,6). The melittin peptide possesses numerous biological properties, but the hemolytic action of the melittin peptide limits the clinical applications of the protein (2).…”

Section: Introductionmentioning

confidence: 99%

Construction of the plasmid coding for the expression of the EGFP-M-IL-2(88Arg, 125Ala) fusion protein and the anti-tumor effects exerted by the fusion protein in HeLa-60 cells

et al. 2015

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Abstract. Gene therapy is a promising therapeutic option for the treatment of various cancers, and tumor-targeted plasmids encoding toxic protein genes are potential tools for gene therapy. In the present study, a recombinant plasmid containing the genes for the toxic protein melittin and interleukin-2 (IL-2) was constructed. Melittin and IL-2 are known to play key roles in immunoregulation and cancer therapy, but they each possess defects that limit the clinical application of these proteins. The present study aimed to construct a novel recombinant expression plasmid, pLEGFP-C1-M-IL-2(

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“…Previous experiments have demonstrated that the upregulation of MMP expression is closely associated with the migration of smooth muscle cells ( 3 ). Thus, the use of MMP inhibitors may significantly reduce the migration and proliferation of smooth muscle cells ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of monocyte-endothelium interactions on the expression of type IV collagenases in monocytes

Liu

Xue

et al. 2014

Experimental and Therapeutic Medicine

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The adhesion of monocytes to endothelial cells is one of the early stages in the development of atherosclerosis. The expression of type IV collagenases, which include matrix metalloproteinase (MMP)-2 and MMP-9, in monocytes is hypothesized to play an important role in monocyte infiltration and transformation into foam cells. The aim of the present study was to examine the effects of monocyte-endothelium interactions on the expression levels of type IV collagenases and their specific inhibitors in monocytes, and to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in this process. Monocytes were single-cultured or co-cultured with endothelial cells. The expression of the type IV collagenases, MMP-2 and MMP-9, and their specific inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, in monocytes was determined by immunohistochemistry followed by image analysis. The expression levels of MMP-2 and MMP-9 were found to be low in the single-culture monocytes, but increased significantly when the monocytes and endothelial cells were co-cultured. However, treatment with monoclonal TNF-α or IL-1β antibodies partially inhibited the upregulated expression of MMP-2 and MMP-9 in the co-cultured monocytes. Expression of TIMP-1 and TIMP-2 was observed in the single monocyte culture, and a small increase in the expression levels was observed when the monocytes were co-cultured with endothelial cells. Therefore, monocyte-endothlium interactions were shown to increase the expression of type IV collagenases in monocytes, resulting in the loss of balance between MMP-2 and -9 with TIMP-1 and -2. In addition, TNF-α and IL-1β were demonstrated to play important roles in this process.

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

Cited by 25 publications

References 37 publications

Protective effect of Xin Mai Jia ultrafiltration extract on human umbilical vein endothelial cell injury induced by hydrogen peroxide and the effect on the NO-cGMP signaling pathway

Protective effect of Xin Mai Jia ultrafiltration extract on human umbilical vein endothelial cell injury induced by hydrogen peroxide and the effect on the NO-cGMP signaling pathway

Construction of the plasmid coding for the expression of the EGFP-M-IL-2(88Arg, 125Ala) fusion protein and the anti-tumor effects exerted by the fusion protein in HeLa-60 cells

Effects of monocyte-endothelium interactions on the expression of type IV collagenases in monocytes

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