• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.197-203
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• 2005

Purpose : Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines. Methods : Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-${\alpha}$ were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones. Results : Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was $36.8{\pm}2.8pg/mL$ and TNF-${\alpha}$ $2.2{\pm}2.7pg/mL$ in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-${\alpha}$(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-${\alpha}$ in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group. Conclusion : These results suggested a potential role for TNF-${\alpha}$ in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.338-349
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• 1999

Polymorphonuclear leukocytes(PMN) are the predominant inflammatory cells recruited in acute lung injury such as adult respiratory distress syndrome, pneumonia and also chronic lung disease such as idiopathic pulmonary fibrosis and pulmonary emphysema. Interleukin-8(IL-8) is an 8,000 D protein produced by many cells and has potent neutrophil chemoattractant and activating properties. The GRO, also called melanoma growth-stimulatory activity(MGSA), referring to a peptide of 73 amino acids, was reported to be mitogenic for cultured human melanoma cells. Mature GRO/MGSA has marked sequence similarity to IL-8. In view of the structural similarities to IL-8, it was of particular interest to test GRO for neutrophil activating and chemotactic properties. We found a significant release of IL-8 and GRO/MGSA from the cultured human umbilical vein endothelial cell(HUVEC) which was stimulated either with TNF$\alpha$ or IL-1$\beta$ and also found the expression of IL-8 and GRO/MGSA mRNA. Neutrophil chemotactic activity was enhanced in accordance with the increased IL-8 and GRO/MGSA. Our study also suggest that the IL-8 is more important in the increased neutrophil chemotactic activity than GRO/MGSA when endothelial cell is stimulated with TNF$\alpha$ or IL-1$\beta$ in vitro.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.293.2-293.2
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• 2002

Bisphenol A ［BPA. 2.2-bis(4-hydroxyphenyl)propane］ is reported to have estrogenic activity: however. its influence on cytokine production or immune system function remains unclear. In this study. we investigated the effects of BPA on the production of nitric oxide (NO) and tumor necrosis factor-a (TNF-a), and on the level of inducible nitric oxide synthase (iNOS) and TNF-a gene expression in mouse macrophages. BPA alone did not affect NO or TNF-a production. (omitted)

• BMB Reports
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• v.40 no.2
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• pp.290-294
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• 2007

Saxatilin is a disintegrin known to inhibit tumor progression in vivo and in vitro. The role of saxatilin in cancer cell invasion was examined by a modified Boyden chamber assay in MDAH 2774 human ovarian cancer cell line. Saxatilin (50 nM) significantly inhibited cancer cell invasion induced by tumor necrosis factor-$\alpha$ (TNF-a$\alpha$). Saxatilin also reduced MMP-9 mRNA levels in cancer cells in a dosedependent manner. In addition, TNF-$\alpha$-induced MMP-9 activity was reduced by the treatment of saxatilin. These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.369-376
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• 2008

In the present study, we investigated the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl) on irradiated rat lungs to determine its potential as a radioprotective agent. We found that early lung damage induced by irradiation was reduced by treatment with 40mg/kg of cyclo(L-phenylalanyl-L-prolyl) in the latent and early pneumonitis phases. Expression of $TNF-{\alpha}\;and\;TGF-{\beta}1$ at 2 and TGF-${\beta}1$ at 8 weeks post-irradiation was decreased in animals that received both radiation and cyclo(L-phenylalanyl-L-prolyl) compared with animals that received radiation alone. Evidence indicated that the proinflammatory cytokine TNF-${\alpha}$ and the fibrogenic cytokine TGF-${\beta}1$ likely play a role in the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl). However, besides TNF-${\alpha}$ and TGF-${\beta}1$ expressions, the precise mechanism by which cyclo(L-phenylalanyl-L-prolyl) ameliorates the induced radiation damage is not clear.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.367-370
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• 2001

This study describes the synthesis and in vitro evaluation of noble 2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone Derivatives for the inhibition of TNF-$\alpa$ production. Among these compounds, 2- [3- (Cyclopentyloxy)- 4- methoxyphenyll- 3- methyl -1 - isoindolinone (5) was the most potent in inhibitory activity of TNF-$\alpa$ production in LPS-stimulated RAW264.7 cells.

• Journal of Ginseng Research
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• v.20 no.1
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• pp.15-22
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• 1996

In order to investigate the Immunomodulatory effects of ginseng, we have studied the effects of ginseng saponin on the proliferation and cytosine gene expression of human pheripheral blood mononuclear cell (PBMC). In the PBMC proliferation assay, total saponin exhibited proliferation inhibition on the PBMC or phytohemagglutinin(PHA)-stimulated PBMC in a dose-dependent fashion. Immunomodulatory effects of ginseng were further investigated using the cytokine gene expression as the indicators. In the reverse transcription-polymerase chain reaction (RT-PCR) test, interleukin (IL)-1, IL-2, IL-3, IL-4, IL-6, IL-13, granulocyte macrophage-colony stimulating factor, tumor necrosis factor (TNF), migration inhibitory factor and transforming growth factor genes were expressed in the PHA-stimulated PBMC 48 hrs after cell culture. Among expressed cytokines, total saponin could increase the expression of IL-1 and TNF of PBMC without stimulation of PHA. All of ginsenosides, $Rb_1$, $Rb_2$, $Rg_1$, Rc, Re, incresed TNF gene expression. Especially, Rb2 (20 g/ml) showed most prominent effect on TNF gene expression and it also slightly increased IL-1 gene expression of PBMC.

• The Journal of Pediatrics of Korean Medicine
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• v.22 no.1
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• pp.95-102
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• 2008

Objectives The purpose of this study was to examine the anti allergic reaction with Cheonmaec-tang. Methods We examined Cell Viability, ${\beta}$-hexosaminidase, TNF-${\alpha}$, IL-4 secretion from RBL-2H3 cell after pretreatment with 2 ㎎/ml, 4 ㎎/ml of Cheonmaec-tang. Results We observed that Cheonmaec-tang is reduced to ${\beta}$-hexosaminidase, TNF-${\alpha}$, IL-4 secretion in RBL-2H3 cell. Conclusions These results indicate that Cheonmaec-tang has anti-histamic effect and controls TNF-${\alpha}$, IL-4 secretion on allergic reaction.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.5
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• pp.978-982
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• 1997

In order to investigate the immunomodulatory mechanism of Ganoderma lucidum, the effects of protein-bound polysacchride of Ganoderma lucidum on the proliferation and cytokine gene expression of mouse peritoneal macrophages was studied. In the macrophage proliferation assay using the BrdU labeling reagent, the GLA component extracted from Ganoderma lucidum or GLB from the bud of Ganoderma lucidum were added to the medium at the concentration of 0 to 256ug/ml. DNA synthesis of the macrophage was increased at 16ug/ml of GLA and 64ug/ml of GLB, respectively. In the reverse transcription polymerase chain reaction(RT-PCR), the cytokine(TNF, IL-1, and IL-12) gene and $\beta$-actin expression were also analyzed. 20$\mu\textrm{g}$/ml of either GLA or GLB increased TNF and IL-1 expression of the macrophages.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.5
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• pp.283-287
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• 2003

While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.