• Toxicological Research
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• v.13 no.3
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• pp.203-208
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• 1997

The antigenic potential of M3S tumor necrosis factor-$\alpha$(M3S TNF), which is a mutated form of TNF(TNF mutein) designed to reduce adverse effects of wild type human TNF, was investigated in the present study. The antigenicity of M3S TNF was examined by conducting active systemic anaphylaxis (ASA) test in guinea pigs, heterologous(mouse-rat) passive cutaneous anaphylaxis(PCA) test and passive hemagglutination(PHA) test. The experimental animals were divided into low, medium, high and the highest dose groups and the groups with or without immunoadjuvant, sensitized according to the appropriate schedule and challenged. In ASA test, when challenged with 120 $\mu\textrm{g}$ /animal, moderate to severe positive anaphylactic responses were observed in groups sensitized with 12 $\mu\textrm{g}$ /animal, 120 $\mu\textrm{g}$ /animal and 120 $\mu\textrm{g}$ /animal+Freund's complete adjuvant. In PCA test, positive responses were observed in the group sensitized with the highest dose emulsified with an alum(12 $\mu\textrm{g}$ /animal+alum). In PHA test, positive responses were observed in the group sensitized with 3 $\mu\textrm{g}$ /animal emulsified with an alum. All the other groups in each experiment showed negative responses. Based on these results, M3S TNF is considered to have some antigenic potential.

• Restorative Dentistry and Endodontics
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• v.36 no.1
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• pp.26-36
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• 2011

Objectives: In the present study, three kinds of tissues cells (pulp, gingiva, and periodontal ligament) were investigated if those cells express MMP and TIMP when they were stimulated with neuropeptides (substance P, CGRP) or proinflammatory cytokine, TNF-$\alpha$. Materials and Methods: The cells cultured from human dental pulp (PF), gingiva (GF) and periodontal ligament were (PDLF) stimulated with Mock, SP, TNF-$\alpha$, and CGRP for 24 hrs and 48 hrs. for an RNase protection assay and Enzyme Linked Immunosorbent Assay. Cells (PF, GF and PDLF) seeded in 100 mm culture dish were stimulated with SP ($10^{-5}$, $10^{-8}\;M$) or only with medium (Mock stimulation) for 4hrs and for 24 hrs for RNase Protection Assay, and they were stimulated with CGRP ($10^{-5}\;M$) and TNF-$\alpha$(2 ng/mL) for 24 hrs and with various concentraion of TNF-$\alpha$(2, 10, and 100 ng/mL) for Rnase Protection Assay with a human MMP-1 probe set including MMP 1, 2, 8, 7, 8, 9, 12, and TIMP 2, 3. In addition, cells (PF, GF and PDLF) were stimulated with Mock and various concentraion of TNF-$\alpha$(2, 10, and 100 ng/mL) for 24 hrs and with TNF-$\alpha$(10 ng/mL) for 48 hrs, and the supernatents from the cells were collected for Enzyme Linked Immunosorbent Assay (ELISA) for MMP-1 and MMP-13. Results: The expression of MMPs in PF, GF, PDLF after stimulation with SP and CGRP were not changed compared with Mock stimulation for 4 hrs and 24 hrs. The expression of MMP-1, -12, -13 24 hrs after stimulation with TNF-$\alpha$ were upregulated, however the expression of TIMP-3 in PF, GF, PDLF after stimulation with TNF-$\alpha$ were downregulated. TNF-$\alpha$(2 ng/mL, 10 ng/mL, 100 ng/mL) increased MMP-1 and MMP-12 expression in PF dose dependently for 24 hrs. Conclusions: TNF-$\alpha$ in the area of inflammation may play an important role in regulating the remodeling of dentin, cementum, and alveolar bone.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

• Journal of Convergence for Information Technology
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• v.10 no.5
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• pp.232-238
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• 2020

This study evaluated the anti-aging activity with antioxidant, anti-inflammatory and moisture activity of Ganoderma lucidum spore oil(GLS). GLS increased DPPH radical scavenging activity in a dose-dependent manners. Anti-inflammatory assay measured the inhibitory effect of GLS on NO, TNF-α and IL-6 production in LPS-stimulated RAW264.7 cells. As a result GLS inhibited NO and pro-inflammatory cytokine, TNF-α, IL-6 production. Also using human fibroblast cell to the procollagen production analysis and COL1A1 mRNA expression level analysis for defining, and for AQP-3 mRNA expression level analysis, used human keratinocyte cell. GLS increased procollagen production and COL1A1, AQP-3 mRNA expression. Our results suggest that the GLS have potential anti-inflammatory and wrinkle improves, skin moisture effect.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.797-807
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• 2004

This research investigates the effect of the Hibiscus syriacus(HSS) on Alzheimer's disease. The effects of the HSS extract on the behavior in the Morris water maze experiment; the expression of IL-1β, TNF-α, IL-1β mRNA, TNF-α mRNA, CD68/GFAP and RDS; the the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with M were investigated. The HSS extract group showed a significant inhibitory effect on the memory deficit on the mice with Alzheimer's disease induced by βA in the Morris water maze experiment. The HSS extract group suppressed the over-expression of IL-1β, TNF-α, IL-1β and TNF-α mRNA, CD68/GFAP, RDS in the mice with Alzheimer's disease induced by βA. The HSS extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by βA. This study suggest that HSS may be effective for the prevention and treatment of Alzheimer's disease

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.176-176
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• 1998

An enhanced formation of nitric oxide (NO) is an important mediator of hypotention, peripheral vasodilation and vascular hyporeactivity to vasoconstrictor agents in endotoxaemia. And tumor necrosis factor (TNF${\alpha}$), as a primary mediator of circulatory shock has been known to induce inducible nitric oxide synthase (i-NOS), leading to excessive production of NO. We isolated two sesquiterpene lactone compounds from Saussurea lappa and their structures were elucidated as dehydrocostus lactone and costunolide. These compounds inhibit the production of both NO and TNF${\alpha}$ by LPS (1 $\mu\textrm{g}$/$m\ell$)-activated Raw 264.7 cells. NO was measured spectropho-tometrically as nitrite by the Griess reagent and TNF${\alpha}$ by ELISA. Dehydrocostus lactone (IC$\sub$50/ : 3.0 ${\mu}$M) and costunolide (IC$\sub$50/ : 4.5 ${\mu}$M) inhibited the production of NO in LPS-activated Raw 264.7 cells by suppressing inducible nitric oxide synthase enzyme expression. These compounds also decreased the TNF${\alpha}$ levels in LPS-activated system in vitro and in vivo.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1353-1365
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF -resistance in TNF-$\alpha$ cDNA transfected cancer cells would be. an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of MnSOD, an antioxidant enzyme, in the acquired resistance to TNF of TNF-$\alpha$ cDN A transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and the changes of MnSOD mRNA expressions with Northern blot analysis. Results : The MnSOD mRNA expressions of parental cells and genetically modified cells of WEHI164 and ME180 cells(both are naturally TNF sensitive) were not significantly different The MnSOD mRNA expressions of genetically modified cells of NCI-H2058 and A549(both are naturally TNF resistant) were higher than those of the parental cells, while those of parental cells with exogenous TNF were also elevated. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the MnSOD expression, but the difference in natural TNF sensitivity of each cell may be associated with the level of the MnSOD expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1795-1804
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• 2004

This research investigated the effect of the Chaenomelis fructus(CMF) on Alzheimer's disease. The effects of the CMF extract on the behavior in the Morris water maze experiment; the expression of IL-1β, TNF-α, ROS on the microglial cell; IL-1β mRNA, TNF-α mRNA, CD68/GFAP and MDA on the brain tissue; the infarction area of the hippocampus, and brain tissue injury in the mice with Alzheimer's disease induced by βA were investigated. The CMF extract group showed a significant inhibitory effect on the memory deficit on the mice with Alzheimer's disease induced by βA in the Morris water maze experiment. The CMF extract group suppressed the over-expression of IL-1β, TNF-α, IL-1β and TNF-α mRNA, ROS, MDA, CD68/GFAP in the mice with Alzheimer's disease induced by βA. The CMF extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by [3A. This study suggest that CMF may be effective for the prevention and treatment of Alzheimer's disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.1
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• pp.150-155
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• 1994

In order to evaluate the effect of the extracts of eidble and medicinalplant son the activation of immune cells, measurements were made by ELISA and radioimmunoassay on the degree of release for the tumor necrosis factor (TNF) and neopterin by the edible and medicinal plants in peripheral blood cells. The results of measurements of TNF in the supernatant cultured liquid showed nothing in t도 control which does not have any edible and medicinal plants. However, measurements of TNF 9pg/ml) in the samples are given as follows : 716.7 in lipopolysaccharide (LPS 1 g/ml), 465.2 Rheum plamatum L.m302.7 Sanguisorba offciinalis L. 818.2 Rubus coreanus M, 328.3 Terminalia chebula R., 426.6 AReca catechu L. 227.0 Eugenia caryophiliata T., 272.9 Ephedra sinica S., 30.1 Caesalpinia sappan L., 474.0 Chaenomeles japonica L., 396.0 Cornus officinalis S.in edible and medicinalplants. ENopterin (n mole/L) value showed below the check point in the control group, however, the values are 11.0 in LPS, and edible and medicinal plants, 5.3 Rheum palmatum L., 11.6 Eugenia caryophiliata T., 5.5 Ephedra sinica S., 4.5 Caesalpinia sappan L., 4.3 Chaenomelees japonica L.3.7 Cornus officinalis S. In order to find m RNA levels of Cytokines increased by edible and medicinal plants, total RNA was separated from mononuclear cells treated 5 hrs with Rubus coreanus M. and then administrated for RT-PCR. The considerable increases of the m RNA of TNF, IL-1 $\alpha$ and IL-6 were observed.

• Journal of Oriental Neuropsychiatry
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• v.17 no.2
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• pp.91-122
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• 2006

Objective : This research investigates the effect of the Jangwon-Dan,(JWD) on Alzheimer's disease. Method : The effects of the JWN extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA, the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, and $TNF-{\alpha}$ mRNA, (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Result : 1. The JWN extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-1 cells treated with LPS. 2. The JWN extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The JWN extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the JWN extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The JWN extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and CD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The JWN extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusion : These results suggest that the JWN extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the JWN extract for Alzheimer's disease is suggested for future research.