• Biomolecules & Therapeutics
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• 제12권1호
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• pp.1-8
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• 2004

In chronic airway inflammatory diseases such as asthma and chronic bronchitis, it has been suggested that matrix metalloproteinases secreted from infiltrating neutrophil contribute the pathogenesis of the disease and have been a focus of intense investigation. We report here that hamster tracheal surface epithelial goblet cells (HTSE cells) produce matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2). Matrix metalloproteinase activities were investigated using [$^3H$]collagen-digestion assay and gelatin zymography. The subtype of matrix metalloproteinases expressed from HTSE cells was MMP-2 (gelatinase A), which was determined by Western blot with various subtype selective anti-matrix metalloproteinase antibodies. The MMP-2 and TIMP-2 cDNAs from HTSE cells were partially cloned by RT-PCR and they reveal more than 90% of sequence homology with those from human, rat and mouse. The collagenolytic activity was increased with the secretory differentiation of the HTSE cell and it was found that zymogen activation was responsible for the increased MMP-2 activity in HTSE cells. The results from the present study suggest that the metaplastic secretory differentiation of airway goblet cells may affect chronic airway inflammatory process by augmenting the zymogen activation of MMP-2.

• 대한의생명과학회지
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• 제10권2호
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• pp.143-151
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• 2004

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, a process that is necessary for angiogenesis, tumor invasion and metastasis. Platelet-activating factor (PAP) increases angiogenesis, tumor growth and metastasis through nuclear factor (NF)-$\kappa$B activation. Based on these facts, the involvement of MMPs in PAF-induced pulmonary metastasis was investigated in murine sarcoma cells, MMSV-BALB/3T3. Messenger RNA expression and enzymatic activity of MMP-9 were assessed by RT-PCR and zymography, and cell migration and metastasis were done for the detection of MMP-9 functional activity. PAP induced mRNA expression and enzymatic activity of MMP-9, and its effects were either inhibited by the PAP antagonist, WEB 2170 or by the NF-$\kappa$B inhibitor, parthenolide, or p65 antisense oligonucleotide in a dose-dependent manner. In addition, PAF induced promoter activity of MMP-9, which was inhibited by WEB 2170, phenanthroline, NAC, PDTC. These results indicate that PAF induces mRNA expression and enzymatic activity of MMP-9 in NF-$\kappa$B dependent manner. Cell migration assay showed that PAF induced MMSV-BALB/3T3 migration, and its effect was significantly inhibited by treatment with phenanthroline. PAF enhanced pulmonary metastasis of murine sarcoma cells, MMSV-BALB/3T3 was also reduced by phenanthroline. These results suggest that PAF-enhanced cell migration and pulmonary metastasis is mediated through the expression of MMP. In conclusion, It is suggested that PAF enhances pulmonary metastasis by inducing MMP-9 expression via the activation of NF-$\kappa$B.

• 대한화장품학회지
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• 제30권2호
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• pp.247-251
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• 2004

자외선은 피부에 염증반응이나 광노화와 같은 다양한 반응을 야기시킨다고 알려져 있다. 특히 자외선에 의해 손상을 받은 피부는 콜라겐의 양이 감소되어 있는데, 이는 자외선에 의해 피부 내에서 콜라겐을 분해하는 효소(MMP, matrix metalloproteinases)의 양이 증가하기 때문이라고 알려져 왔다. 또한 자외선에 의해 피부에서 염증반응이 유발되는데, 이러한 반응은 프로스타글란딘이라는 물질에 의해 매개되며, 이 프로스타글란딘에 의해서도 MMP가 증가한다고 알려져 왔다. 본 연구에서는 6개월의 임상실험을 통해 광노화된 피부에서 주름형성억제효능이 뛰어난 FDP(fructose 1.6-diphosphate)의 작용기전을 인체각질형성 세포를 이용하여 연구하였다. 인체각질형성세포에 자외선을 조사할 경우 프로스타글란딘, COX-2(cyclooxygenase-2), MMPs의 활성이 증가하는 것을 확인하였며, 이는 FDP의 처리에 의해 감소되었다. 이러한 효과는 자외선에 의해 인체각질형성세포에서 발생하는 신호전달과정을 억제함으로써 일어나는 효과임이 증명되었다. 따라서, FDP는 자외선에 의해 일어나는 세포 내 신호전달과정을 억제하며, 이로 인해 야기되는 프로스타글란딘, COX-2, MMPs의 증가를 억제함으로써 피부의 광노화를 억제할 수 있는 원료로 여겨진다.

• Natural Product Sciences
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• 제18권1호
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• pp.52-59
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• 2012

In our continuous efforts to procure the active materials from natural products in the protective effects of oxidative stress or UV damage to skin cells we found the Prunus persica flesh extract (PPFE) is considerable to meet the demand to protect the skin damage. PPFE attenuated cell damage induced by hypoxanthine-xanthine oxidase in cultured human keratinocytes, indicating that PPFE has the potential of the scavenging effect of reactive oxygen species (ROS) in human skin cell. Moreover, PPFE significantly suppressed UVA-induced ROS production determined by the oxidation of 2,7-dichlorodihydrofluorescein diacetate (DCFH) using FACS analysis. Additional study revealed that UVA irradiation of HaCaT human keratinocytes increased the gelatinolytic activities of matrix metalloproteinase-2, and -9 (MMP-2, -9) and mRNA expression of MMP-9 analyzing by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and these events were significantly suppressed by the treatment with PPFE. These results suggest that PPFE might be applicable as natural ingredients for skin antiaging agents via UV-induced ROS scavenging activity and suppression of MMP expression in the skin cells.

• 동의생리병리학회지
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• 제31권2호
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• pp.105-110
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• 2017

Prolonged exposure to solar ultraviolet A (UVA) radiation has been known to cause premature skin aging (photo-aging). UVA radiation generates ROS thereby induce degenerative changes of skin such as degradation of dermal collagen, elastic fibers. Matrix metalloproteinases (MMPs), the proteolytic enzymes have been implicated as a major player in the development of UVA-induced photo-aging. Many studies have been conducted to block the harmful effects of UV radiation on the skin. Recently, we are interested in the availability of fermented red ginseng (FRG) as natural matrix metalloproteinases inhibitors (MMPIs). The efficacy difference between red ginseng and FRG has been compared. Both RG and FRG have no cytotoxic effects below the concentration of $300{\mu}g/ml$. Human dermal fibroblasts (HDFs) were pretreated with FRG or RG for 24h, followed by irradiation of UVA. Then, we measured the intracellular ROS production and the expression of MMP, $IL-1{\beta}$ at the mRNA level. We also examined the intracellular localization of $NF-{\kappa}B$ and MMP-9 on the FRG or RG treated and UVA-irradiated HDFs. FRG decreased the intracellular ROS production elicited by UVA. In addition, FRG decreased the mRNA expression of MMP-3, MMP-9, and $IL-1{\beta}$ more efficiently than RG. Furthermore, FRG suppressed the nuclear localization of $NF-{\kappa}B$, and the expression of MMP-9. Taken together, our results suggest that FRG is promising agents to prevent UVA-induced photo-aging by suppressing MMP expression and inflammation.

• International Journal of Industrial Entomology and Biomaterials
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• 제46권2호
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• pp.60-66
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• 2023

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases and is more common in older and obese individuals. Silkworm male pupae exerts tonic effects by increasing testosterone secretion and the forced swimming time and muscle ratio increased in mice consuming silkworm pupae, which may be beneficial to the older population. Therefore, it will be beneficial to investigate the effects of silkworm pupal extracts (SPE) on OA. To confirm this effect, we prepared SPE in different solvents, and their ability to attenuate matrix metalloproteinases (MMPs) and inflammatory mediators (interleukin-6 [IL-6], interleukin-8 [IL-8] and tumor necrosis factor-α [TNF-α]) were evaluated in an interleukin-1β (IL-1β)-induced SW1353 human chondrosarcoma cell line. 70% ethanolic SPE outperformed the other solvents, reducing MMP-1 and MMP-3 expression by up to 53% and 13%, respectively. Further experiments were performed using 70% ethanolic SPE from three distinct pupation stages in males and females. SPE treatment alleviated MMP-1 expression (43.9-47.4%) regardless of pupation stage and sex. Among the inflammatory mediators, 70% ethanolic SPE alleviated IL-6 and TNF-α levels, and the concentrations thereof were lowest in the early-stage male SPE-treated group (43.15% and 56.74%, respectively). In conclusion, 70% ethanolic SPE may prevent IL-1β-induced osteoarthritis by inhibiting MMPs and inflammatory cytokines. Therefore, SPE is a potential therapeutic agent for the treatment of OA.

• BMB Reports
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• 제43권1호
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• pp.62-68
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• 2010

Matrix Metalloproteinases (MMPs) are a family of zinc-endopeptidases which can degrade extracellular matrix (ECM) components and play important roles in a variety of biological and pathological processes. 6,6'-bieckol isolated and characterized from an edible marine brown alga Ecklonia cava (EC), according to the comprehensive spectral analysis of MS and NMR data. Here the influence of 6,6'-bieckol on expressions of MMPs was examined by zymography and western blot analysis via human fibrosarcoma cell line (HT1080). It is shown that 6,6'-bieckol significantly down regulated the expressions of MMP-2 and -9 in dose-dependent manner. The influence of 6,6'-bieckol on the cell viability and cell behavior of HT1080 cells were also investigated, our dates shown that it suppressed the migration and 3D culture in HT1080 cells. Meanwhile, we explored several signal pathways which may contribute to this process, and found the suppressing of MMPs expressions in HT1080 cells might be due to the suppression of NF-${\kappa}B$ signal pathway.

• Tuberculosis and Respiratory Diseases
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• 제64권1호
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• pp.22-27
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• 2008

연구배경: 본 연구에서는 황색포도알균이 숙주세포 내로 침입하여 증식하는 정도를 관찰하고자 한다. 이때 세포 외 바탕 단백질의 변화가 수반될 것으로 가설을 설정하고, 이러한 변화에 영향을 미칠 것으로 생각되는 matrix metalloproteinase (MMP)의 발현과 역할에 대해 연구하고자 하였다. 방법: 황색포도알균은 $10^6{\sim}10^7CFU/ml$을 $10^5$개의 기관지상피세포인 BEAS-2B 세포에 2시간 동안 침입시킨다. 이후 세척으로 세포 밖에 있는 황색포도알균을 제거한 후, BEAS-2B 세포를 다양한 시간 동안(4, 6, 8, 12 시간) 배양한 후 황색포도알균의 집락수(CFU/ml)를 측정하였고, 단백질을 분리하여 세포 외 바탕단백질의 발현 정도와 MMP의 활성도를 측정하였다. 또한 MMP 억제제인 GM6001을 전처치한 후 황색포도알균을 세포에 침입시킨 후 세포 내에서의 균의 집락수 및 세포 외 바탕단백질의 변화를 관찰하였다. 결과: 황색포도알균의 집락을 측정한 결과 4시간과 12시간을 비교해 볼 때 MOI가 증가할수록, 감염시킨 시간이 길수록 숙주세포 내로 침입이 유의하게 증가하였다. BEAS-2B 세포에서 황색포도알균을 침입시킨 시간이 길수록, MOI가 증가할수록 MMP 2 및 MMP 9의 활성도와 dysadherin의 발현은 증가하였고, 이와는 대조적으로 E-cadherin의 발현은 감소하였다. MMP억제제인 GM6001을 전 처치 한 결과 황색포도알균의 세포 내 침입을 유의하게 감소시켰다. 결론: 황색포도알균이 기관지 상피세포 내로 침입할 때 dysadherin 및 E-cadherin 같은 세포 외 바탕 단백질의 변화를 동반하며, MMP 활성도가 균의 세포 내 침입에 관여하는 것으로 보인다.

• BMB Reports
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• 제28권1호
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• pp.33-39
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• 1995

The Gelatinases (typeIV collagenases) are metalloproteinases that may play an important role in tumor invasion and metastasis. Progelatinase A was purified from a conditioned medium of T98G human glioblastoma cells. TIMP-2 complexed progelatinase A and free progelatinase A were separated by heparin affinity HPLC. The final product was homogeneous on SDS-PAGE, with a molecular weight of 64,000 daltons without reduction. TIMP-2 and free progelatinase A were separated from TIMP-2 complexed progelatinase A by reverse-phase HPLC in the presence of trifluoroacetic acid. TIMP-2 complexed progelatinase A was resistant to activation by p-aminophenyl mercuric acetate (APMA), and showed less than 20% of the activity of the TIMP-2 free active enzyme. TIMP-2 free progelatinase A was easily activated to the mature form with a molecular weight of 57,000 daltons by APMA and showed high activity compared to the TIMP-2 complexed enzyme.

• Restorative Dentistry and Endodontics
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• 제37권1호
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• pp.2-8
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• 2012

The limited durability of resin-dentin bonds severely compromises the longevity of composite resin restorations. Resin-dentin bond degradation might occur via degradation of water-rich and resin sparse collagen matrices by host-derived matrix metalloproteinases (MMPs). This review article provides overview of current knowledge of the role of MMPs in dentin matrix degradation and four experimental strategies for extending the longevity of resin-dentin bonds. They include: (1) the use of broadspectrum inhibitors of MMPs, (2) the use of cross-linking agents for silencing the activities of MMPs, (3) ethanol wet-bonding with hydrophobic resin, (4) biomimetic remineralization of water-filled collagen matrix. A combination of these strategies will be able to overcome the limitations in resin-dentin adhesion.