• The Journal of the Korean Society for Microbiology
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• v.35 no.1
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• pp.9-18
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• 2000

Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5301-5310
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• 2013

The biological mechanisms of cancer and associations with behavior of tumours need to be studied to understand progression and determine appropriate treatments. Here we investigated expression of VEGF, MMP-9 and E-cadherin in laryngeal SCCs and their relations with clinical behavior. This prospective study was based on 38 surgical specimens from patients with primary laryngeal SCC and data recorded in their cards. Expression of the three factors in tumor tissue was examined using immunohistochemistry and correlations with clinical parameters of primary tumors, regional lymph node metastases, stage of disease, histopathologic differentiation, and vascular/cartilage invasion were investigated. Regarding the cases with positive MMP-9 expression, the difference between well and moderately/poorly differentiated tumors was statistically significant. However, differences between early stage (stage I and II) and late-stage (stage III and IV) tumours, and between positive and negative for pLN metastasis were not. No significant relationship between positive VEGF and tumor differentiation or stage was apparent, but E-cadherin levels significantly differed between well and moderately/poorly differentiated tumours and with the presence of pLN metastasis. E-cadherin staining did not vary between MMP-9 positive and negative cases. In conclusion, MMP-9 may be a negative predictor of differentiation in laryngeal SCC, while E-cadherin is a predictor of differentiation and nodal metastases. Even if the difference between VEGF expression and tumor stage was not statistically significant, it seems that there exists some relationship, which might be clarified with a greater number of cases.

• Journal of Life Science
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• v.18 no.4
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• pp.503-508
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• 2008

Deep sea water from the East sea was tested for breast cancer chemoprevention and metastasis by measuring the activities of cytochrome P450 1A1 and aromatase, invasiveness, and activity and expression of matrix metalloproteinase (MMP)-9 in breast MDA-MB-231 cancer cell. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity. Deep sea water showed 27.1, 45.4 and 51.9% inhibition of microsomal aromatase activity at the hardness of 600, 800 and 1,000, respectively. In addition deep sea water inhibited not only the invasiveness of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MDA-MB-231 cells through matrigel-coated membrane in a hardness-dependent manner but also the activity and expression of MMP-9 in MDA-MB-231 cell.

• Perinatology
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• v.29 no.4
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• pp.170-174
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• 2018

Objective: Progesterone is used to prevent recurrent preterm delivery, however the molecular mechanisms of its effect are incompletely understood. The objective of this study was to determine the effect of progesterone on tumor necrosis factor $(TNF)-{\alpha}$-induced matrix metalloproteinase (MMP)-9 activity in human choriodecidual (CD) membranes. Methods: We collected CD membranes from women with uncomplicated term pregnancies who were scheduled for elective cesarean delivery (n=10). CD membranes ($1{\times}1cm$) were incubated in tissue culture media at $37^{\circ}C$. We pre-treated the CD membranes with progesterone (P4), $17{\alpha}$-hydroxyprogesterone caproate (17P), promegestone (R5020), or vehicle (ethanol) for 24 hours. The CD membranes were subsequently treated with $TNF-{\alpha}$ (with continued progesterone treatment) for 48 hours, then media was harvested for measuring MMP-9 activity by zymography and total protein was isolated from CD membrane tissues for MMP-9 expression by western blot analysis. Results: P4, 17P, and R5020 significantly reduced $TNF-{\alpha}$-induced MMP-9 activity in fetal membrane tissue samples (P=0.0078, P=0.0156, and P=0.0391, respectively) by zymography. Western blot analysis also showed decreased expression of MMP-9 in progesterone pretreated groups (P=0.0313). Conclusion: Progesterone reduces $TNF-{\alpha}$-induced MMP-9 activity in human CD membranes. These findings may provide further support for the role of progesterone in preventing preterm birth.

• Journal of Embryo Transfer
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• v.27 no.2
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• pp.93-100
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• 2012

To investigate the biochemical nature of changes in vaginal physiology during estrus and pregnancy, we examined the cytology and viscosity, and monitored the protein expression profile in vaginal mucus during estrus and pregnancy. The viscosity progressively decreased from estrus to pregnancy. Cell type analysis revealed that white blood cells progressively increased from estrus to pregnancy, while red blood cells progressively decreased during pregnancy. The cornification index (CI) was higher in estrus than in pregnancy. Protein mass spectrumetry identified the presence of ribosome-binding protein 1, GRIP 1 (Glutamate receptor-interacting protein 1)-associated protein 1, DUF729 (Domain of unknown function729) domain-containing protein 1, prolactin precursor, dihydrofolatereductase, and MMP (Matrix metalloprotease)-9 in vaginal mucus. MMP-2 and MMP-9 proteins in the vaginal mucus were active throughout estrus and gestation, as measured by a gelatinase assay, but most abundant in the vaginal mucus on day 0 of estrus. Results from ELISA of MMP-2 and MMP-9 were in accordance with the gelatinase assay. In light of the crucial role of metalloproteinases in extracellular matrix remodeling, the level of MMP-9 in vaginal mucus might be useful as an indicator of estrus and pregnancy to increase the efficiency of reproduction.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.131-146
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• 1998

To examine the effect of Shiquandabutang on the metastasis of cancer, the following experiments were made. Before the main experiments, the cytotoxicity was measured by putting Shiquandabutang sample in HT1080. Then zymography was made to examine the change of gelatinolytic activity. And western blotting was carried out to examine the changes of Fos, Jun, Ets, the transcription factors of MMP-2, MMP-9, and Erk, JNK on signal transduction pathway to AP-1. Third, in vitro invasion assay with transwells coated by collagen and matrigel was carried out. From the results of the above the following conclusions were obtained. 1. The experimental result about cytotoxicity of Shiquandabutang against HT1080 was as below. The stained cell count after being treated by Shiquandabutang sample $400{\mu}g/ml$ for 24 hours was 0.9% of total cells, and the stained cell count by Shiquandabutang sample $100{\mu}g/ml$ was 1.5% of total cells. Both were near the level of control group which showed 0.6% stained. 2. The result of collagenase assay was as below. In Shiquandabutang sample $400{\mu}g/ml$, MMP-2 was reduced as compared with TPA control group, and the band of MMP-9 induced by TPA disappeared. In Shiquandabutang sample $800{\mu}g/ml$, both bands of MMP-2 and MMP-9 disappeared. 3. The results of western blots for Jun, Fos, Ets, Erk, JNK were as below. In Shiquandabutang sample $200{\mu}g/ml$, Ets was reduced, and Fos were increased. 4. The result of invasion assay was as below. The number of cells which migrated across transwell membrane in Shiquandabutang-treated group was less than that of +TPA control group. From the above results, it was concluded that Shiquandabutang might control the appearing and acting of collagenase not by the MMP-2, -9 promoter but by other way.

• Journal of Periodontal and Implant Science
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• v.37 no.1
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• pp.23-33
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• 2007

파골세포에 의한 골흡수는 1) 혈관을 통한 파골세포 전구세포의 골표면 이동 및 2) 골표면에서 파골세포 전구세포로부터 파골세포 분화 두 단계를 거쳐 일어난다. Stromal cell derived factor $(SDF)-1{\alpha}$ 는 파골세포 전구세포의 화학주성인자이며 matrix metalloproteinase (MMP)-9는 파골세포 전구세포의 이동에 관여하는 단백 분해효소이다. 파골세포 전구세포의 골표면 이동에 있어서 LPS의 역할을 규명하기 위하여 E. coli 및 Actinobacillus actinomycetecomitans LPS의 1) 파골세포 전구세포 유도능, 2) LPS에 의한 파골세포 전구세포의 이동에 있어서 MMP 및 $SDF-1{\alpha}$ 의 관련성을 평가하였다. LPS에 의한 차골세포 전구세포의 RAW 세포의 이동은 matrigel 또는 type I collagen을 도포한 transwell을 이용하여 평가하였으며 MMP-9 및 $SDF-1{\alpha}$ 의 발현은 RT=PCR 또는 ELISA로 평가하였다. 각 세균의 LPS는 matrigel 또는 type I collagen을 통한 파골세포 전구세포의 이동을 증가시켰다. MMP 억제제는 각 세균의 LPS에 의한 파골세포 전구세포의 이동을 억제하였다. LPS는 파골세포 전구세포의 MMP-9의 발현을 증가시켰다. 각 세균의 LPS는 마우스 두개골에서 분리한 조골세포의 $SDF-1{\alpha}$ 의 발현을 증가시켰다. $SDF-1{\alpha}$ 을 함유한 LPS 처리 조골세포 배양상층액은 파골세포 전구세포의 이동을 증가시켰으며 anti $SDF-1{\alpha}$ Ab는 LPS처리 세포 배양상층액에 의한 파골세포 전구세포의 이동을 억제하였다. 이들 결과는 LPS가 파골세포 전구세포에서는 MMP-9을 조골세포에서는 $SDF-1{\alpha}$ 의 발현을 증가시켜 파골세포 전구세포의 이동을 촉진 시킬 수 있음을 시사한다.

• Journal of Pharmacopuncture
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• v.21 no.3
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• pp.177-184
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• 2018

Objectives: Auraptene, a natural citrus coumarin, found in plants of Rutaceae and Apiaceae families. In this study, we investigated the effects of auraptene on tumor migration, invasion and matrix metalloproteinase (MMP)-2 and -9 enzymes activity. Methods: The effects of auraptene on the viability of A2780 and Hela cell lines was evaluated by MTT assay. Wound healing migration assay and Boyden chamber assay were determined the effect of auraptene on migration and cell invasion, respectively. MMP-2 and MMP-9 activities were analyzed by gelatin zymography assay. Results: Auraptene reduced A2780 cell viability. The results showed that auraptene inhibited in vitro migration and invasion of both cells. Furthermore, cell invasion ability suppressed at $100{\mu}M$ auraptene in Hela cells and at 25, $50{\mu}M$ in A2780 cell line. Gelatin zymography showed that for Hela cell line, auraptene suppressed MMP-2 enzymatic activity in all concentrations and for MMP-9 at a concentration between 12.5 to $100{\mu}M$ in A2780 cell line. Conclusion: Auraptene inhibited migration and invasion of human cervical and ovarian cancer cells in vitro by possibly inhibitory effects on MMP-2 and MMP-9 activity.

• Archives of Plastic Surgery
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• v.34 no.2
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• pp.149-155
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• 2007

Purpose: This study was to investigate how the heparin, which has been known to induce neovascularization by MMP in the infarcted tissue of the myocardium, had influence on the expression of mRNA of MMP 1,2,9 of the skin wound of rat. Methods: Full depth skin wounds were created on the dorsum of Sprague-Dawley 60 rats. The experimental rats were divided into two groups according to the concentration of heparin($100{\mu}g/ml$ in 20, $300{\mu}g/ml$ in 20). Heparin soaked gelatin sponges in different concentration were inserted into the pocket of experimental rats and the wounds were closed. Normal saline soaked gelatin sponges were used in control rats. Wounds were harvested at 48 and 72 hours after closure. We performed histologic study in H-E stain. RNA was isolated from the harvested tissue and then real time polymerase chain reaction was performed to determine the gene expression of MMP-1,2,9. Results: We observed that inflammatory cell decreased in heparin soaked group and heparin increased the expression of MMP-1,9 mRNA of dorsal wound of rat at 72 hours (p < 0.05). Conclusion: This result suggest that heparin may be used inducing another factor inducing scarless wound healing by increasing MMP.

• Journal of Life Science
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• v.25 no.9
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• pp.1000-1006
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• 2015

α-Asarone is the main component of Acorus gramineus, which is a widely used oriental traditional medicine. A. gramineus is known to have a variety of medicinal effects, such as anti-gastric ulcer, antiallergy and antioxidant activity. It is also known to inhibit the release of histamine. However, the mechanism of its action remains unclear in humans. In this study, the effects of α-asarone on matrix metalloproteinase (MMP) and its antioxidant effect in a cell-free system were examined in HT1080 cells. In an MTT assay, the effect of α-asarone on cell viability showed no cytotoxicity below 16 μM. In an antioxidant assay, α-asarone increased reducing power in a dose-dependent manner but not the scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In addition, α-asarone exhibited the protective effect against DNA oxidation induced by hydroxyl radicals produced by the Fenton reaction. Furthermore, in a gelatin disk assay, α-asarone enhanced collagenase activity. It also increased the activities of MMP-2 and MMP-9 stimulated by phorbol 12-myristate 13-acetate (PMA) in a gelatin zymography. On the other hand, the activity of MMP-9 stimulated by phenazine methosulfate (PMS) but not that of MMP-2 was increased in the presence of α-asarone. These findings suggest that α-asarone could be a candidate for the prevention and treatment of pathological diseases related to oxidative stress and MMPs.