• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.619-634
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• 2002

Background : Many inflammatory mediators and collagenases are involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The increase of matrix metalloproteinase-9 (MMP-9, gelatinase-B) produced mainly by inflammatory cells was reported in many ALI models and connective tissue cells. In this study, the expression of MMP-9 in ventilator-induced lung injury (VILI) model and the effects of matrix metalloproteinase inhibitor (MMPI) on VILI were investigated. Methods : Eighteen Sprague-Dawley rats were divided into three groups: low tidal Volume (LVT, 7mL/Kg tidal volume, 3 $cmH_2O$ PEEP, 40/min), high tidal volume (HVT, 30mL/Kg tidal volume, no PEEP, 40/min) and high tidal volume with MMPI (HVT+MMPI) groups. Mechanical ventilation was performed in room air for 2 hours. The 20 mg/Kg of CMT-3 (chemically modified tetracycline-3, 6-demethyl 6-deoxy 4-dedimethylamino tetracycline) was gavaged as MMPI from three days before mechanical ventilation. The degree of lung injury was measured with wet-to-dry weight ratio and acute lung injury score. Expression of MMP-9 was studied by immunohistochemical stain with a mouse monoclonal anti-rat MMP-9 $IgG_1$. Results : In the LVT, HVT and HVT+MMPI groups, the wet-to-dry weight ratio was $4.70{\pm}0.14$, $6.82{\pm}1.28$ and $4.92{\pm}0.98$, respectively. In the HVT group, the ratio was significantly higher than other groups (p<0.05). Acute lung injury score measured by five-point scale was $3.25{\pm}1.17$, $12.83{\pm}1.17$ and $4.67{\pm}0.52$, respectively. The HVT group was significantly damaged by VILI and MMPI protects injuries by mechanical ventilation (p<0.05). Expression of MMP-9 measured by four-point scale was $3.33{\pm}2.07$, $12.17{\pm}2.79$ and $3.60{\pm}1.95$, respectively, which were significantly higher in the HVT group (p<0.05). Conclusion : VILI increases significantly the expression of MMP-9 and MMPI prevents lung injury induced by mechanical ventilation through the inhibition of MMP-9.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.422-429
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• 2009

Invasion and metastasis is the main cause of cancer mortality. Angiogenesis is a prerequisite for the tumor growth and metastasis. Matrix metalloproteinases (MMPs) are the key enzymes playing in the invasive growth and metastasis of cancer as well as angiogenesis. Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L), has been reported to suppress cancer invasion and angiogenesis. In the present study, we investigated the antiinvasive effects of xanthohumol (1) and its synthetic derivatives, 4'-O-methylxanthohumol SEM ether (2), xanthohumol C (3), and xanthohumol C MOM ether (4) in relation to MMP expression in HT-1080 human fibrosarcoma cells. The compound 1 and its derivative, 3 and 4, significantly inhibited serum-induced HT-1080 cell invasion, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced activity and expression level of MMP-2 and MMP-9 in a concentration-dependant manner. In addition, they inhibited TPA-enhanced expression of MT1-MMP with relatively weak inhibition in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 level. The compound 1 significantly decreased the cell viability, whereas the derivatives, 2 and 3 showed no cytotoxicity, and compound 4 showed slight cytotoxicity in the cells. Furthermore, in a chick chorioallantoic membrane (CAM) assay, the derivatives 3 and 4 dose-dependently suppressed vascular endothelial growth factor (VEGF)-induced angiogenesis, which is similar to that of compound 1. Taken together, the results indicate that compounds 3 and 4 may be valuable anti-angiogenic agents in the treatment of chronic diseases such as cancer and inflammation working through suppression of MMP-2 and MMP-9.

• Nutrition Research and Practice
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• v.6 no.6
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• pp.499-504
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• 2012

This study attempted to investigate the effects of resveratrol on the differentiation of adipocytes. After cells were treated with various concentrations of resveratrol (0, 10, 20, and 40 ${\mu}mol/L$), adipocyte proliferation, the protein expression of transcription factors, and MMPs' activities were determined. Cell proliferation was inhibited more within 4 days of incubation (P<0.05), and lipid accumulation in adipocyte was significantly inhibited by 93.8%, 92.4% and 91.5%, respectively, after two days of 10, 20, and 40 ${\mu}mol/L$ resveratrol treatment (P<0.05). Six days of incubation with the three resveratrol concentrations caused a significantly decreases of 63%, 59.9%, and 25.1% GPDH activity as a dose-dependent response. The triglyceride concentration also decreased significantly with the increase of resveratrol concentration (P<0.05). The protein expression of CCAAT/enhancer-binding protein (C/$EBP{\beta}$) was decreased significantly by 56% and 30% while $PPAR{\gamma}$ was significantly reduced by 57% and 15% with resveratrol treatments of 20 and 40 ${\mu}mol/L$, respectively (P<0.05). The protein expression of C/$EBP{\alpha}$ was decreased by 83%, 74%, and 38% to increased dosage levels, with significance determined for this decrease from 20 ${\mu}mol/L$ of resveratrol. The protein expression of fatty acid binding protein (FABP4) was decreased significantly by 88%, 72%, and 46% with the increase of resveratrol concentration. The activity of MMP-2 was decreased significantly by 84%, 70%, and 63% while MMP-9 activity was decreased significantly by 74%, 62%, and 39% with the increased resveratrol concentrations of 10, 20, and 40 ${\mu}mol/L$, respectively (P<0.05).

• Korean Journal of Food Science and Technology
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• v.50 no.6
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• pp.653-659
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• 2018

In this study, we investigated the antioxidant activities and anti-aging efficacy in terms of suppression of matrix metalloproteinases (MMPs) in UVB-irradiated HaCaT cells by adding the ethanol extracts of Josaengheogchal (JE) and Shintoheug rice (SRE). In the electron-donating ability and ABTS radical-scavenging assays, we observed that both JE and SRE had scavenging activities and in a collagenase inhibition assay, both extracts showed inhibition effects of over 73% at $1,000{\mu}g/mL$ concentration. The expression of MMP-1 and -3, when the extracts were treated with UVB $50mJ/cm^2$, irradiated human HaCaT keratinocytes, was analyzed by western blotting and reverse-transcription polymerase chain reaction (RT-PCR). The results showed that MMP-1 and -3 proteins and mRNAs were downregulated in a concentration-dependent manner in response to both extracts. Therefore, we expect that these compounds have a potential for the use as functional ingredients with anti-aging effects in the cosmetic and food industries.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.449-456
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• 2004

Phytoestrogens derived from plants and foods, which are diphenolic compounds with structural similarities to natural and synthetic estrogens, have been shown to estrogenic and antiestrogenic actions. Particularly, recent study revealed that phenolic compounds in safflower seed, such as serotonin derivatives, lignans and flavonoids, could be acted as phytoestrogens. Safflower (Carthamus tinctorius L.) seed extract (SID C.SE), therefore, are receiving a renewed interest as potential therapeutic source against skin wrinkles induced by estrogen deficiency. This study was conducted to investigate the anti-wrinkle effect of SID C.SE on normal human fibroblasts through the expression of type I procollagen and UVA-induced MMP-1 in vitro. The SID C.SE increased the type I procollagen expression, comparable to trans-retinol and reduced UVA-induced MMP-1 expression in a dose-dependent manner. The clinical study indicated that cream group treated with $0.1\%$ SID C.SE significantly reduced a skin wrinkles, as compared with a control (non-treated cream group) (p<0.05). These results suggest that the safflower seed extract may be useful as potential source of anti-wrinkle cosmetics.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.19 no.3
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• pp.229-242
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• 2018

The effects of orally administered fermented porcine placenta (FPP) and its major dipeptides, L-Leucyl-Glycine (Leu-Gly) and Glycyl-L-Leucine (Gly-Leu), on UVB-induced wrinkle formation of the skin in hairless mice was studied. Treatment with FPP, Leu-Gly or Gly-Leu increased type I procollagen synthesis and decreased MMP-1 (matrix metalloproteinase-1) in human dermal fibroblast cells (HDF-N). Hairless mice were also exposed UVB irradiation three times a week and fermented porcine placenta extract (FPP), Leu-Gly and Gly-Leu was administered once a day for eight weeks. Daily intake of FPP, Leu-Gly and Gly-Leu for eight weeks decreased wrinkles, erythema and thickness of the skin and increased skin hydration and synthesis of collagen relative to a UVB-control. Moreover, FPP, Leu-Gly or Gly-Leu intake decreased the expression of MMP-3 and MMP-13 mRNA levels and inhibited activation of MMP-2 and MMP-9 induced by UVB irradiation in hairless mice skin. These results suggest that major dipeptides of the placenta, Leu-Gly and Gly-Leu have the potential for use as a functional food ingredient with anti-wrinkling properties.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.133-140
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• 2002

To evaluate the anti metastatic effect of Antivascular-first(AntiV-F), we investigated cytotoxic effect on B16-F10 and HMCB. gene expression of MMP-9 and nm23-H1, and survival. After treating with AntiV-F, AntlV-F promoted cytotoxic effect on B16-F10 and HMCB as its density, compared with Control. AntiV-F inhibited gene expression of MMP-9 in the L+14 and HMCB cell line compared with Control. On the other hand AntiV-F increases gene expression of nm23-H1 and survival about 30% compared with Control. These results suggest that AntiV-F has effects on anti-metastasis can be used for treatment of cancer patients and preventing recurrence.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.28 no.1
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• pp.31-41
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• 2002

The production of matrix matalloproteinases(MMPs) by the UV irradiated skin fibroblast and the degradation of extracellular matrix(ECM) by these enzymes is known as one of the main reasons of photoaging. Recently, Fisher group showed that the MMP expression is mainly regulated by the mitogen-activated protein(MAP) kinas family, such as extracellular signal-regulated kinase(ERK), c-Jun amino-terminal kinase(JNK) and p38, each of which forms a signaling pathway. In this work we first examined the effect of nitric oxide (NO) on the production of MMP-1 and MMP-2 by the human dermal fibroblasts (HDFs). NO is a multifunctional messenger molecule generated from L-arginine and involved in many kinds of signaling pathway. We found that the treatment of HDF with NO donor, sodium nitroprusside (SNP) enhanced the expression of MMPs with or without UV irradiation and the treatment with nitric oxide synthase (NOS) inhibitors resulted in the significant decrease of MMPs production. From these results, we concluded that the production of MMPs by the UV irradiated HDF is regulated through the signaling pathway involving NO and cyclic GMP.

• Nutrition Research and Practice
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• v.7 no.3
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• pp.160-165
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• 2013

3T3-L1 preadipocyte were differentiated to adipocytes, and then treated with 0, 10, 20, and $40{\mu}g/mL$ of peanut sprout ethanol extract (PSEE). The main component of PSEE is resveratrol which contained 5.55 mg/mL of resveratrol. The MTT assay, Oil-Red O staining, glycerol-3-phosphate dehydrogenase (GPDH) activity, and the triglyceride concentration were determined in 3T3-L1 cells. MMP-2 and MMP-9 activities as well as mRNA expressions of C/EBP ${\beta}$ and C/EBP ${\alpha}$ were also investigated. As the concentration of PSEE in adipocytes increased, the cell proliferation was decreased in a dose-dependent manner from 4 days of incubation (P < 0.05). The GDPH activity (P < 0.05) and the triglyceride concentration (P < 0.05) were decreased as the PSEE treatment concentration increased. The mRNA expression of C/EBP${\beta}$ in 3T3-L1 cells was significantly low in groups of PSEE-treated, compared with control group (P < 0.05). The MMP-9 (P < 0.05) and MMP-2 (P < 0.05) activities were decreased in a dose-dependent manner as the PSEE concentration increased from $20{\mu}g/mL$. In conclusion, it was found that PSEE has an effect on restricting proliferation and differentiation of adipocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.201-208
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• 2013

Objective: To investigate changes in the invasive capacity of gastric cancer cells in vitro after expression inhibition of T lymphoma invasion and metastasis inducing factor 1 (Tiam 1) and underlying mechanisms. Methods: Using adhesion selection, two subpopulations with high ($M_H$) or low ($M_L$) invasive capacity were separated from the human gastric cancer cell line MKN-45 ($M_0$). Tiam 1 antisense oligodeoxynucleotide (ASODN) was transfected into $M_H$ cells with liposomes, and expression of Tiam 1 mRNA and protein was determined by RT-PCR and quantitative cellular-ELISA. Changes in the cytoskeleton, invasive capacity in vitro and expression of ras-related $C_3$ botulinum toxin substrate 1 (Rac 1), integrin ${\beta}1$ and matrix metalloproteinase 2 (MMP 2) between Tiam 1 ASODN transfected $M_H$ cells and non-transfected cells were observed by HE staining, cytoskeletal protein staining, scanning electron microscopy, Boyden chamber tests and cyto-immunohistochemistry. Results: A positive correlation existed between the expression level of Tiam l mRNA or protein and the invasion capacity of gastric cancer cells. After ASODN treatment ($0.43{\mu}M$ for 48 h), Tiam 1 mRNA transcription and protein expression in $M_H$ cells were decreased by 80% and 24% respectively (P < 0.05), compared with untreated controls, while invasive capacity in vitro was suppressed by 60% (P < 0.05). Morphologic and ultrastructural observation also showed that ASODN-treated $M_H$ cells exhibited smooth surfaces with obviously reduced filopodia and microspikes, which resembled $M_0$ and $M_L$ cells. Additionally, cytoskeletal distribution dramatically altered from disorder to regularity with reduced long filament-like structure, projections, pseudopodia on cell surface, and with decreased acitn-bodies in cytoplasm. After Tiam 1 ASODN treatment, the expression of Rac 1 and Integrin ${\beta}1$ in $M_H$ cells was not affected (P > 0.05), but that of MMP 2 in $M_H$ cells was significantly inhibited compared with untreated cells (P < 0.05). Conclusion: Over-expression of Tiam-1 contributes to the invasive phenotype of gastric cancer cells. Inhibition of Tiam 1 expression could impair the invasive capacity of gastric cancer cells through modulating reconstruction of the cytoskeleton and regulating expression of MMP 2.