• Development and Reproduction
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• v.14 no.3
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• pp.207-214
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• 2010

The tremendous changes of uterine endometrium are observed during early pregnancy and protease and their inhibitors are involved in regulation of cell proliferation and remodeling of the tissues through remodeling the extracellular matrix (ECM). Some of the proteases and protease inhibitors have been suspected to a factor in endometrial changes but many parts of their expression profiles and the physiological roles are not uncovered. To evaluate the functional roles of them, in this study the expression profiles of proteases and protease inhibitors were analyzed using real-time quantitative PCR analysis. Mmp9 (matrix metalloproteinase 9) mRNA levels peaked on day 4 at the time of implantation. On the other hand, Ela2 (neutrophil elastase, NE) mRNA levels were peaked on day 2 of pregnancy. Its expression were decreased until day 4 of pregnancy but increased rapidly until day 7 of pregnancy and decreased again. NE inhibitor Slpi (secretory leukocyte protease inhibitor, SLPI) mRNA levels were related with the implantation stage and with the levels of Ela2. At the time of implantation the expression levels of Slpi mRNA were about 5 times higher than the Ela2 mRNA in the uterus. In the implantation stage embryos, Mmp9 specific mRNA was only detected at the blastocyst. On the other hand, the expression level of SLPI was higher than that of the Ela2 mRNA at blastocyst and 4.5 day p.c. embryos. Based on these results it is suggested that MMP9, SLPI, and NE have important physiological role in embryo implantation both in uterus and embryos.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• Biomedical Science Letters
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• v.15 no.4
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• pp.309-317
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• 2009

Occupational exposure to inorganic dusts such as coal and silica has been identified as a chronic obstructive pulmonary disease (COPD) risk factor. This risk factor causes lung inflammation and protease-antiprotease imbalance. This abnormal inflammatory response of the lung induces parenchymal tissue destruction and leads to progressive airflow limitation that is characteristics of COPD. The aim of this study was to determine the relationship of proteases such as neutrophil elastase (NE) and matrix metalloproteinase (MMP)-9 and antiproteases such as alpha-1 antitrypsin (AAT) and tissue inhibitors of metalloproteinase (TIMP)-1 with lung function. The study population contained 223 retired workers exposed to inorganic dusts. We performed lung function test, including percent of forced expiratory volume in one second ($%FEV_1$) predicted and $%FEV_1$/forced vital capacity (FVC). We analyzed serum MMP-9, AAT, TIMP-1 and plasma NE concentrations by sandwich enzyme immunoassay. NE, AAT, and TIMP-1 concentrations in workers, who had $%FEV_1$<80% predicted, were higher than those of workers who had $%FEV_1{\geq}80%$ (P<0.05). Both AAT and TIMP-1 concentrations in workers with airflow limitation were higher than those of workers with normal airflow (P<0.05). $%FEV_1$ predicted showed significant negative correlation with AAT (r=-0.255, P<0.0l), TIMP-1 (r=-0.232, P<0.01), and NE (r=-0.196, P<0.01). $%FEV_1$/FVC predicted showed significant negative correlation with NE (r=-0.172, P<0.05). From the results of stepwise multiple regression analysis about $%FEV_1$ and $%FEV_1$/FVC, significant independents were NE (r=-0.135, P=0.001) and AAT (r=-0.100, P=0.013) in $%FEV_1$, and NE (r=-0.160, P=0.014) in $%FEV_1$/FVC. In the present study, there were significant correlations between airflow limitation and protease concentration and between airflow limitation and antiprotease concentration. Serum protease and antiprotease concentrations, however, may be affected by the biological and inflammatory responses. It is necessary to evaluate specimens more reflected the effects of proteases and antiproteases in the lung such as lung tissue, bronchoalveolar lavage fluid, and exhaled breath condensate (EBC).

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.172-179
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• 2011

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.