• Molecules and Cells
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• v.25 no.1
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• pp.105-111
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• 2008

Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor $(TGF)-{\beta}1$ led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of $TGF-{\beta}$ receptor I kinase, abolished $TGF-{\beta}1$- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via $TGF-{\beta}$ signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.

• Food Science of Animal Resources
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• v.35 no.2
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• pp.164-170
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• 2015

The objective of this study was to evaluated the photoprotective effects of porcine placenta extract (PPE) on ultraviolet B (UVB)-induced oxidative stress in human keratinocytes (HaCaT) to evaluate its functional activities as a skin food ingredient. PPE prepared by subcritical water extraction was termed SPE, and subsequently digested by enzymes to prepare E-SPE. Increased intracellular reactive oxygen species (ROS) levels (192.0%) induced by UVB were decreased by SPE and E-SPE. SPE had more effective ROS scavenging activity than E-SPE treatment. UVB treatment increased expression of tissue inhibitor of metalloproteinase 1 (TIMP-1), and this elevated expression was decreased by E-SPE treatment. High-dose treatment with E-SPE (50 and 100 µg/mL) reduced TIMP-1 expression levels of UVB-C (control) to 33.5 and 34.6%, respectively. In contrast, at low SPE doses (1 and 10 µg/mL), the treatment slightly decreased TIMP- 1 expression levels to 73.3% and 71.3% of UVB-C, respectively. In conclusion, the present study demonstrated the protective effect of SPE and E-SPE against UVB damage in keratinocytes via ROS scavenging, down-regulating MMP-2 expression and up-regulating TIMP- 1 expression. This highlights the potential for SPE as an ingredient in the preparation of functional food against photoaging.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.2 s.57
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• pp.81-88
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• 2006

Amino acid complex was made with the composition of amino acids quite similar to that of stratum corneum on the skin. In order to evaluate the efficacy of amino acid complex on the skin as an active cosmetic ingredient, we measured cytotoxicity. TIMP-1 expression, moisturizing effect and the amount of horny substance. In cytotoxicity assay, amino acid complex did not show any cytotoxicity. In moisturizing effect test using corneometer, it showed very good moisturizing effect. In TIMP-1 mRNA assay using RT-PCR, moo acid complex showed the increase of TIMP-1 expression, suggesting that amino acid complex have anti-wrinkle effect. Therefore, amino acid complex may be useful as an active ingredient for anti-aging.

• Tuberculosis and Respiratory Diseases
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• v.77 no.2
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• pp.73-80
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• 2014

Background: Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. Methods: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-$1{\beta}$ (IL-$1{\beta}$) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D ($1,25(OH)_2D$) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. Results: IL-$1{\beta}$ significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and $1,25(OH)_2D$ (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and $1,25(OH)_2D$. Conclusion: Vitamin D, 25(OH)D, and $1,25(OH)_2D$ play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-$1{\beta}$ stimulated MMP-9 production and conversion to its active form but also inhibiting IL-$1{\beta}$ inhibition on TIMP-1 and TIMP-2 production.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.144-149
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• 2009

Chondrocytes and synovial fluid derived markers are used to monitor for osteoarthritis(OA). Specific inhibitors, known as tissue inhibitors of metalloproteinases(TIMP), regulate the proteolytic activity of matrix metalloproteinases(MMP). This study investigated whether MMP and TIMP levels were altered in synovial fluid and cartilage following the experimental induction of OA in canines. Twenty mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and the medial collateral ligament as well as a medial meniscectomy. Matrix metalloproteinase-2 and MMP-9 levels were assayed using Western blot and TIMP-2 levels were measured with enzyme-linked immunosorbent assays four weeks after OA induction. Increased MMP-2 expression was observed in chondrocytes isolated from cartilage following OA induction, but MMP-9 expression decreased. Matrix metalloproteinase-2 and MMP-9 levels in synovial fluid from the OA induced joint significantly increased compared to those of the sham group. Tissue inhibitors of metalloproteinase-2 concentrations were higher in chondrocytes from the OA cartilage, yet TIMP-2 remained lower in the synovial fluid of OA. This suggests the elevated release of MMP-9 over MMP-2 into the synovial fluid following the cartilage degradation-related death of chondrocytes after OA. Osteoarthritis can be further deteriorated by increased MMP activity in the synovial fluid because TIMP-2 exist low concentration into the extracellular matrix. As a result, MMP activity, particularly MMP-9 activity, can be useful as a biomarker in diagnosing and monitoring the early stages of canine OA.

• Journal of Periodontal and Implant Science
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• v.41 no.3
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• pp.109-116
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• 2011

Purpose: The purpose of this study was to compare and quantify the expression of C-reactive protein (CRP), matrix metalloproteinase (MMP)-14, and tissue inhibitor of metalioproteinases (TIMP)-2 in gingival tissues of patients with chronic periodontitis accompanied with inflammatory reaction related to alveolar bone resorption with or without type 2 diabetes mellitus (DM). Methods: Twelve patients with type 2 DM and chronic periodontitis (group 3), twelve patients with chronic periodontitis (group 2), and twelve healthy individuals (group 1) were included in the study. Gingival tissue biopsies were collected from each patient and from healthy individuals at the time of periodontal surgery (including surgical crown lengthening) or tooth extraction. The concentrations of cytokines were determined by a western blot analysis. Results: The expression levels of CRP and MMP-14 increased in group 2 and 3, and they were highest in group 3. The expressions of TIMP-2 also increased in group 2 and 3. Conclusions: This study demonstrated that the expression levels of CRP, MMP-14, and TIMP-2 might be inflammatory markers in periodontal inflamed tissue. It can be assumed that CRP, MMP-14, and TIMP-2 may be partly involved in the progression of periodontal inflammation associated to type 2 DM.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.325.3-326
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• 2002

An imbalance between matrix metalloproteinase (MMP)-2 and its endogenous inhibitor. tissue inhibitor of metalloproteinase (TIMP)-2 causes the degradation of the extracellular matrix associated with pathological events including invasion. metastasis and angiogenesis. Since TIMPs are secreted molecules. they have the potential to be used for gene therapy of certain tumors. (omitted)

• Journal of Periodontal and Implant Science
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• v.40 no.1
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• pp.33-38
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• 2010

Purpose: The purpose of this study was to observe and quantify the expression of interleukin-4 (IL-4), interferon-$\gamma$ (IFN-$\gamma$), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the gingival tissue of patients with type 2 diabetes mellitus (DM) and healthy adults with chronic periodontitis. Methods: Twelve patients with type 2 DM and chronic periodontitis (Group 3), twelve patients with chronic periodontitis (Group 2), and twelve healthy individuals (Group 1) were included in the study. Clinical criteria of gingival (sulcus bleeding index value, probing depths) and radiographic evidences of bone resorption were divided into three groups. The concentrations of cytokines were determined by a western blot analysis and compared using one-way ANOVA followed by Tukey's test. Results: The expression levels of IFN-$\gamma$ and TIMP-2 showed an increasing tendency in Groups 2 and 3 when compared to Group 1. On the other hand, the expression of IL-4 was highest in Group 1. Conclusions: The findings suggest that IFN-$\gamma$ and TIMP-2 may be involved in the periodontal inflammation associated with type 2 DM. IL-4 may be involved in the retrogression of the periodontal inflammation associated with type 2 DM.

• Journal of Periodontal and Implant Science
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• v.46 no.2
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• pp.84-95
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• 2016

Purpose: The objective of this study was to investigate the effect of a dietary flavonoid, kaempferol, which has been shown to possess antiallergic, anti-inflammatory, anticarcinogenic, and antioxidant activities on the periodontium by histomorphometric analysis and on gingival tissue matrix metalloproteinase-1 (MMP-1), MMP-8, and tissue inhibitor of metalloproteinase-2 (TIMP-2) by biochemical analysis of rats after experimental periodontitis induction. Methods: Sixty Wistar rats were randomly divided into six groups of ten rats each, and silk ligatures were placed around the cervical area of the mandibular first molars for 15 days, except in the healthy control rats. In the experimental periodontitis groups, systemic kaempferol (10 mg/kg/2d) and saline were administered by oral gavage at two different periods (with and without the presence of dental biofilm) to all rats except for the ten non-medicated rats. Alveolar bone area, alveolar bone level, and attachment level were determined by histomorphometric analysis, and gingival tissue levels of MMP-1, MMP-8, and TIMP-2 were detected by biochemical analysis. Results: Significantly greater bone area and significantly less alveolar bone and attachment loss were observed in the kaempferol application groups compared to the control groups (P<0.05). In addition, gingival tissue MMP-1 and -8 levels were significantly lower in the kaempferol application groups compared to the control groups and the periodontitis group (P<0.001). There were no statistically significant differences in TIMP-2 levels between the kaempferol and saline application groups (P>0.05). Conclusions: Kaempferol application may be useful in decreasing alveolar bone resorption, attachment loss, and MMP-1 and -8 production in experimental periodontitis.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.143-143
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• 2003