• Nutrition Research and Practice
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• v.5 no.5
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• pp.375-380
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• 2011

This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol$/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 ${\mu}mol$/L within 48 h. Inorganic sulfur significantly decreased cell motility and invasion in the MDA-MB-231 cells in a dose-dependent manner (P<0.05), as determined using a Boyden chamber assay and a Matrigel chamber. The activities of MMP-2 and MMP-9 were significantly reduced by inorganic sulfur in a dose-dependent manner (P<0.05). The inorganic sulfur also significantly inhibited MMP-2 and MMP-9 expression in the cells (P<0.05). These data suggest that inorganic sulfur can suppress cancer cell motility and invasion by inhibiting MMP-2 and MMP-9 activity and gene expression in MDA-MB-231 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.974-979
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• 2009

Proliferation of vascular smooth muscle cell(VSMC) is one of the key features in onset of atherosclerosis and restenosis after vascular surgery such as stent implant. Atherosclerotic plaques are usually composed of collagen, elatsin and smooth muscle cells. Release of matrix metalloproteinases(MMPs) is considered to have correlation with development of atherosclerotic plaques. Based on the hypothesis that MMP inhibition would be helpful in the treatment of atherosclerosis, we investigated inhibition of MMP activity and migration of TNF-$\alpha$-induced human aortic smooth muscle cell(HASMC) by Cinnamomi Ramulus(CC). The result from gelatin zymography showed that CC inhibited MMP-9 activity in a dose-dependent manner. In addition, CC considerably inhibited the migration of HASMC induced by TNF-$\alpha$, while it showed little cytotoxic effect on HASMC. These results suggest that CC can be a potential anti-atherosclerotic agent through inhibition of MMP-9 activity and SMC migration.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.165-170
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• 2004

The production of matrix metalloproteinases (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. In this paper, to investigate the relationship between aging and Selaginella tamariscina extract (STE), we investigated the effects of antioxidant and expression of UVA-induced MMP-1 in human dermal fibroblasts. STE was found to show scavenging activities of radicals and reactive oxygen species (ROS) with the $IC_{50}$/ values of 65.1 $\mu\textrm{g}$/$m\ell$ against 1,1-diphenyl-2-picrylhydrazyl(DPPH) radical and 40.9 $\mu\textrm{g}$/$m\ell$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. UVA induced MMP expression was reduced 75.5% by treatment with STE, and MMP-1 mRNA expression was reduced in a dose-dependent manner. Therefore STE was able to significantly inhibition of MMP expression in protein and mRNA level. All these results suggested that STE may act as an anti-aging agent by antioxidation and reducing UVA-induced MMP-1 production.

• Biomedical Science Letters
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• v.9 no.3
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• pp.123-131
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• 2003

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study hypothesized that a vascular infection with cytomegalovirus (CMV) may induce a chronic inflammatory reaction and activated inflammatory cells may express inflammatory mediators such as cyclooxygenase-2 (COX-2) and matrix metalloproteinases-9 (MMP-9). To confirm the hypothesis, the immunohistochemical stains for CMV late antigen, COX-2, MMP-9, macrophage, and T-lymphocyte were performed on CMV-infected atherosclerotic lesions. The immunoreactivity for COX-2 and MMP-9 was evident in all cases of atherosclerosis along with plaques, mainly in macrophages/foamy cells, intimal and medial smooth muscle cells, and endothelial cells of the intima. Within the intima, the increased immunoreactivity for COX-2 and MMP-9 was colocalized to the area stained with CMV late antigen. Sections from control specimens showed no immunoreactivity for CMV late antigen, COX-2 and MMP-9. These data seem to support the hypothesis that CMV may participate in a pathogenetic mechanism for atherogenesis or progression of atherosclerosis.

• Journal of Microbiology and Biotechnology
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• v.14 no.2
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• pp.379-384
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• 2004

Fibroblast growth factor-2 (FGF-2) is known to modulate numerous cellular functions in various cell types, including cell proliferation, differentiation, survival, adhesion, migration, and motility, and also in processes such as wound healing, angiogenesis, and vasculogenesis. FGF-2 regulates the expression of several molecules thought to mediate critical steps during angiogenesis. This study examines the mechanisms underlying FGF-2-induced cell migration, using human umbilical vein endothelial cells (HUVECs). FGF-2 induced the nondirectional and directional migration of endothelial cells, which are inhibited by MMPs and plasmin inhibitors, and induced the secretion of matrix metalloproteinase-3 (MMP3) and MMP-9, but not MMP-l and MMP-2. FGF-2 also induced the secretion of the tissue inhibitor of metalloproteinase-l (TIMP-I), but not of TIMP- 2. Also, the pan-PKC inhibitor inhibited FGF-2-induced MMP-9 secretion. It is, therefore, suggested that FGF-2 induces the migration of cultured endothelial cells by means of increased MMPs and plasmin secretion. Furthermore, FGF-2 may increase MMP-9 secretion by activating the PKC pathway.

• Journal of Oral Medicine and Pain
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• v.26 no.2
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• pp.95-105
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• 2001

제 4형 콜라젠을 분해하는 MMP-9은 조직 재생에 중요한 역할을 하기 때문에 주목받아 왔는데, 이전의 문헌들에서 PMA에 의해 이 유전자 발현이 강하게 상승발현된다고 알려져 있다. 비록 MMP-9 발현을 조절하는 PMA의 기전이 잘 밝혀지지는 않았지만, 다른 유전자발현에서의 이 phorbol ester의 효과는 c-raf-1-ERK 신호전달통로의 활성에 관해 연구되어 오고 있다. 하지만 이번 연구에서 저자는 MMP-9 발현에서 PMA의 상승효과에는 대개는 스트레스성 자극과 관련된 JNK1 의존성 신호전달과정이 또한 필요하다는 다른 가능성을 조사하였다. 그 결과 JNK 억제재중 하나인 SP 600125가 UM-SCC-1세포주에서 PMA에 의해 유도된 MMP-9 상승발현을 용량의존적으로 억제하는 것으로 나타났고 72시간동안 전처치를 한 경우에 그의 억제효과가 최대이었다. phorbol ester로 처리한 세포에 GAL4 luciferase reporter와 vector를 주입해서 조사한 결과 PMA가 c-Jun transacting 활성을 상승시켰다. 그뿐 아니라 PMA에 의한 MMP-9 촉진자 활성에는 AP-1 motif가 필요하며 이 motif에 c-Jun이 결합하는 것을 EMSA를 통해 확인하였다. 결론적으로 UM-SCC-1 세포주에서 PMA에 의한 MMP9의 증가된 발현은 이미 밝혀진 ERK 경로뿐 아니라 JNK 경로를 통한 결과임이 밝혀져 이 경로를 차단하는 방법이 또하나의 암치료 방향을 제시해주고 있다.

• The Journal of Korean Medicine
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• v.41 no.4
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• pp.12-26
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• 2020

Objectives: The aim of this study is to investigate the mechanisms involved in the anti-inflammatory and anti-tumor effects of Rhus verniciflua Stokes (RVS) on PMA-differentiated human monocytic leukemia THP-1 cells. Methods: Cells were treated with various concentrations of RVS decoction (0-300㎍/ml) for 24, 48, and 72h. Cell viability was evaluated by MTS/PMS assay. The expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, iNOS and COX-2 mRNA and proteins were measured using RT-PCR and western blotting, respectively. Results: RVS suppressed expression of MMP-2 and MMP-9 mRNA. It also down-regulated iNOS and COX-2 mRNA and protein expression. RVS inhibited NF-𝜅B p65 activity and the phosphorylation of Akt and MAPK (ERK and p38 MAPK). Instead, the phosphorylation of JNK is increased at a very low concentration but decreased at higher concentrations. Conclusion: RVS is regarded to inhibit the expression of MMP and TIMP as well as iNOS and COX-2 gene expression via directly inhibiting the activation of NF-𝜅B and phosphorylation of MAPK pathway in THP-1 cells. This suggests RVS have potential to be used as a therapeutic agent for acute myeloid leukemia (AML).

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.420-430
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• 2002

Background : Excessive extracellular matrix (ECM) deposition by airway inflammation is presumed to play an important role in the pathogenesis of worsening airflow obstruction (Ed- acceptable three-word noun) seen during acute exacerbations of chronic bronchitis. Although many proteases can cleave ECM molecules, matrix metalloproteinases (MMPs) and their inhibitors are likely to be the physiologically relevant mediators of ECM degradation. Objectives ; The purpose of this study was to demonstrate that antibiotic treatment can change airway MMPs and TIMP-1 concentrations/levels by controlling airway inflammation in acute exacerbation of chronic bronchitis. Methods : We studied 40 patients, all of whom had an acute exacerbation of chronic bronchitis. The patients were treated with two different antibiotics, moxifloxacin and clarithromycin, in a double-blind manner for 7 days. Sputum samples were induced and collected before and after antibiotic therapy. We measured the sputum concentration of MMP-1,-9, TIMP-1, IL-8 and secretory leukocyte proteinase inhibitor (SLPI) in sputum supernatants by ELISA method. Results : There was no difference after antibiotic treatment in the sputum concentrations of MMP-1,-9, TIMP-1, IL-8 and SLPI between the patients treated with moxifloxacin and those treated with clarithromycin. But the sputum concentrations of TIMP-1, and SLPI, and the TIMP-1/MMP-1 ratio were significantly reduced by the antibiotic therapy. There were significant positive correlations between sputum TIMP-1 levels and IL-8 levels (p<0.01, r=0.751), and between the sputum TIMP-1/MMP-1 ratio and IL-8 levels (p<0.01, r=0.752). The sputum SLPI levels were significantly elevated by antibiotic treatment and were negatively correlated with sputum TIMP-1 levels (p<0.01, r=-0.496) and TIMP-1/MMP-1 levels (p<0.01, r=-0.456). Conclusion : The study shows that the worsening of airway inflammation in acute exacerbation of chronic bronchitis is associated with an imbalance between the concentrations/levels of TIMP-1 and MMPs. Antibiotic treatment can prevent progression of airway narrowing in acute exacerbation of chronic bronchitis by modulation of the protease and anti-protease imbalance.

• The Korea Journal of Herbology
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• v.23 no.2
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• pp.1-8
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• 2008

Objectives : The purpose of this study was to evaluate on the antimicrobial effect on the periodontal pathogens and anti-inflammatory effect of Artemisiae Iwayomogii Herba. Artemisiae Iwayomogii Herba has been used for treating as Artemisiae Capilaris Herba in Korea. Methods : Artemisiae Iwayomogii Herba was prepared by extracting medicinal herb with water. We investigated antimicrobial activity by the minimun inhibitory concentration (MIC) test. We also investigated inhibition of IL-$1{\beta}$-induced collagenase-l(MMP-l), stromelysin-1(MMP-3), interleukin-6 gene expression in human gingival fibroblasts. Results : The antimicrobial effect of Artemisiae Iwayomogii Herba was evaluated with MIC against periodontopathogens; Porphyromonas gingivalis 2561, W50, A7A1-28, 9-14K-1, Prevotella intermedia28, and Actinobacillus actinomycetemcomitans Y4, MICs of Artemisiae Iwayomogii Herba were 0.156 mg/ml, 0.625 mg/ml, 0.313 mg/ml, 1.25 mg/ml, 10 mg/ml and 10 mg/ml. The anti-inflammatory effect of Artemisiae Iwayomogii Herba was evaluated with Influence of herbs on the IL-$1{\beta}$-induced expression of MMP-1, MMP-3, interleukin-6, IL-$1{\beta}$ increased MMP-1, MMP-3, interleukin-6 mRNA levels. Artemisiae Iwayomogii Herba significantly inhibited IL-$1{\beta}$-induced MMP-1, MMP-3, interleukin-6 gene expressions in a dose-dependent manner. Conclusions : These results suggested that Artemisiae Iwayomogii Herba might reduce the excessive proteolytic capacity of the gingival fibroblast during inflammation and could be developed a new drug in periodontitis.

• Tuberculosis and Respiratory Diseases
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• v.64 no.1
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• pp.22-27
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• 2008

Background: Staphylococcus aureus frequently colonizes and infects hospitalized patients. Respiratory infections with Staphylococcus aureus are common in patients with compromised airway defenses. However the mechanisms of S. aureus invasion from colonization to the epithelium are unclear. Cell invasion by S. aureus would require destruction of the extracellular matrix, which is believed to be the result of increased matrix metalloproteinases (MMP) activity. Methods: In this study, respiratory epithelial cells were infected with S. aureus. After removing the extracellular bacteria by washing, the internalized bacteria in the cells were assessed by counting the colonized forming units (CFUs). The cell adhesion proteins, dysadherin and E-cadherin, were evaluated by Western blotting. The MMPs in the bacterial invasion were evaluated by pretreating the cells with GM6001, a MMP inhibitor. Results: The internalization of S. aureus was found to be both time and dose dependent, and the increase in MMP 2 and 9 activity was also dependent on the incubation time and the initial amount of bacterial inoculation. The invasion of S. aureus was attenuated by GM6001 after 12 hours incubation with a multiply of infection (MOI)=50. The expression of dysadherin, a membrane protein, was increased in a time and dose dependent manner, while the expression of E-cadherin was decreased. Conclusion: MMPs may mediate the invasion of S. aureus into epithelial cells.