• Journal of Acupuncture Research
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• v.24 no.3
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• pp.197-205
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• 2007

Objectives : Tumor necrosis factor-${\alpha}$(TNF ${\alpha}$) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis. This study was designed to investigate the relation between TNF-${\alpha}$ gene polymorphism and rheumatoid arthritis in Korean population. Methods : This study was carried out on 103 rheumatoid arthritis patients who fulfilled the American College of Rheumatology 1987 revised criteria for rheumatoid arthritis and 208 healthy control subjects. Blood samples from all subjects were obtained for DNA extraction. The extracted DNA was amplified by polymerse chain reaction(PCR). PCR products were visualized by 2% agarose gel electrophoresis. We investigated the genotyping of TNF-${\alpha}$ by using Pyrosequencing. Results: The genotypes of TNF-${\alpha}$ gene were GG, AG and AA. While the distribution of TNF-${\alpha}$ polymorphism in control subjects was 92.31%, 7.21%, 0.48% respectively, in rheumatoid arthritis patients was 93.20%, 6.80%, 0.00%(GG, AG, AA). There was no statistical significant allelic frequency difference between control and rheumatoid arthritis groups. Conclusions : We concluded that there was no significant association between TNF-${\alpha}$ gene polymorphism and rheumatoid arthritis. However, the findings of this study need to be confirmed in more patients and further studies.

• Natural Product Sciences
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• v.15 no.2
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• pp.55-59
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• 2009

This study for developing a new anti-inflammatory medicine was sought by investigating the antiinflammatory properties of C. indicum L. extract. Rats were treated with either saline (control) or C. indicum L. extract and then injected with LPS. We found that the plasma concentration of IL-1${\beta}$ IL-6, TNF-${\alpha}$and IL-10 peaked at 5h after LPS injection, and the plasma concentration of IL-6 and TNF-${\alpha}$ showed a tendency to decrease, and IL-10 concentration showed a tendency to increase with increasing levels of C. indicum L. extract. In the liver concentration of cytokines at 5 h post LPS injection, IL-1${\alpha}$ and IL-6 decreased with increasing concentration of C. indicum L. extract, however TNF-${\alpha}$ and IL-10 did not differ significantly the treatment groups.

• 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.

• Journal of Acupuncture Research
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• v.18 no.4
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• pp.125-142
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• 2001

Objective : The purpose of this study is to observe the effect of Aqua-acupuncture with Stephania Tetrandra Solution (ST-AS) on arthritis. Methods : The author performde several experimental items : that isgene expression and secretion of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, MMP-2, production of ROS, paw thickness, DTH, weight of spleen, expression of CD4+, CD8+, CD19+ in the spleen, production of IL-6, TNF-${\alpha}$, examination of histology. Results : The obstain results are summarized as follows. 1. IL-$1{\beta}$, IL-6, TNF-${\alpha}$ gene expression of hFLS were significantly inhibited in treatmentgroup, and gene expression of MMP-2 was not inhibited in treatmentgroup. 2. The secretion amount of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ were significantly inhibited in treatmentgroup. 3. Expression of P-38 MAP kinase and production of ROS were inhibited in treatmentgroup. 4. Treatmentgroup were significantly inhibited the incidence of arthritis, hind paw edema, the index of arthritis and DTH of CIA (collagen II-induced arthritis) mice. 5. Treatmentgroup were significantly decreased splenetic weight and the number of CD4+, CD8+, CD19+ activated cells and secretion aroout of IL-6, TNF-${\alpha}$ of CIA (collagen II-induced arthritis) mice.. 6. Treatmentgroup were expressed form of new bone, synoviumin, new margine in histology imperison to controlgroup. Conclusions : Taking all these observations into account, ST-AS injection is considered to be effective in treating arthritis and put to practical use in future arthritis clinic.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.26-30
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• 2007

Background: Mycobacterial antigens released as PIM, LM, LAM, lipoproteins and other cellular factors may contribute to macrophage and dendritic cell activation through pattern recognition receptors such as TLRs. In this study, we assessed cytokine production and ERK activation with stimulation of several major mycobacterial antigens. Methods: Purified mycobacterial antigens (10, 22, 30, 38kDa) and recombinant antigens (6, 16, 19, 38kDa, Ag85A antigen) were studied. The production of cytokines (TNF-${\alpha}$, IL-12, IL-6) was measured by ELISA. The ERK activation was detected by western blotting. The expression of TLR2 or TLR4 was measured by flow cytometry. Results: Among purified antigens only 30kDa antigen induced production of IL-6 or TNF-${\alpha}$ in THP-1 macrophage cells. When THP-1 macrophage cells were treated with 30kDa antigen, phosphorylation of ERK was detected. ERK activation also occurred in TLR2 transfectant HEK293 cells with 30kDa antigen stimulation. Conclusion: 30kDa antigen is one of the major mycobacterial antigens inducing cytokine production and MAP kinases phosphorylation in macrophages.

• The Journal of Korean Physical Therapy
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• v.18 no.6
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• pp.13-21
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• 2006

Purpose: To provide the basic method for physical therapy to contribute to early stage treatment of a burned patients. We investigated whether or not carbon arc lamp treatment and low level laser one among various laser treatments have the effect of reducing Cytokine, and to elucidate the effect of carbon arc lamp treatment and laser one. Methods: The 6-week old BALB/c types of 92 mice were used for the experimental test, and they were burned with $100^{\circ}C$ water, they were divided into 4 groups in accordance with the method of treatment respectively. And the blood and the tissue from the subject of each group were extracted and analyzed each time after they were cured for 3, 6, 9 days. For the analysis of the results, SPSS statistical program was used in this study. Results: The quantity of $TNF-{\alpha}$ and $IL-1{\beta}$ within the blood of a burned mouse increased more than that of a normal mouse(p<0.01). In only a burned mouse, carbon arc lamp treatment gave the effect on the decrease of $TNF-{\alpha}$ thickness the 6th day to the 9th day(p<0.01). $IL-1{\beta}$ quantity was more decreased than that of control group around the 6th day. In comparison with only a control group, low level laser treatment has more significant effect in decreasing the quantity of $TNF-{\alpha}$ a and $IL-1{\beta}$ than the two different methods(p<0.01). In case that the two treatment methods, carbon arc lamp treatment and low level laser, were executed together, there was the effect of decreasing $TNF-{\alpha}$ until the 6th day(p<0.01). Conclusion: Both low level laser treatment and carbon arc lamp one would be able to have an effect on the inflammation inhibition of burned patients and tissues reproduction. However, it must be also considered for the two treatments to be done at the same time.

• Journal of Applied Biological Chemistry
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• v.60 no.3
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• pp.199-205
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• 2017

To investigate the anti-inflammatory activity of natural products, we determined the anti-inflammatory activity of purified epigallocatechin (EGC) from Camellia sinensis leaves. In the present study, we found that EGC inhibited the production of proinflammatory mediators (IL-6, TNF-${\alpha}$, NO, and $PGE_2$) in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. Suppression of IL-6 seems to be at least partly attributable to the inhibitory effect of EGC. TNF-${\alpha}$ is a major cytokine produced by LPS-induced macrophages, and they have a wide variety of biological functions including regulation of inflammation. The inhibition of IL-6 and TNF-${\alpha}$ production by EGC may downregulate the acute-phase response to LPS, thereby reducing LPS-induced inflammation. In addition to IL-6 and TNF-${\alpha}$, EGC effectively reduced the production of other key inflammatory mediators, including NO and $PGE_2$. The inhibitory effect of EGC on NO and $PGE_2$ production was supported by the suppression of inducible nitric oxide synthase and COX-2 at protein levels. These results support the traditional use of EGC in the alleviation of various inflammation-associated diseases and suggest that EGC might be useful in the development of new functional foods for inflammatory diseases.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.137-142
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• 2002

This study describes the synthesis and in vitro evaluation of 2-[3- (Cyclopenthloxy) 4-Methoxyphenyl] - Substituted-1-Isoindolinone derivatives substituted on benzene moiety of isoindoline ring for the inhibition of $TNF-{\alpha}$ production. From this study, we have found the 6-C position on isoindolinone ring is an optimal derivatization site. Among the compounds synthesized, 6-ammo-2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone (6) was the most potent in inhibitory activity of $TNF-{\alpha}$ production in LPS-stimulated RAW264.7 cells.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.87-96
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• 1994

Background : Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around(like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves(like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-$\gamma$ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. Method : We transferred TNF-$\alpha$ gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, I would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. Result : NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-$\alpha$ gene to. Conclusion : TNF-gene-transfer to NCI-H2058 and WEHI164 gave them resistance to TNF.

• Korean Journal of Pharmacognosy
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• v.41 no.2
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• pp.97-102
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• 2010

Six triterpenoid compounds, friedelin (1), $3{\alpha}$-hydroxy-2-friedelanone (2), canophyllol (3), oleanolic aldehyde acetate (4), ursolic acid (5), and pachysandiol A (6) were isolated from the methylene chloride soluble fraction of the roots of A. japonica. The chemical structures of compounds 1-6 were determined by the basis of physico-chemical properties and spectroscopic methods such as 1D and 2D NMR. These compounds were isolated from this plant for the first time. For the isolated compounds (1-3), the inhibitory effect of IL-6 production in TNF-$\alpha$ stimulated MG-63 was examined. Among the isolates, $3{\alpha}$-hydroxy-2-friedelanone (2) showed potent inhibitory effect on IL-6 production in TNF-$3{\alpha}$ stimulated MG-63.