• Journal of the Korean Society of Physical Medicine
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• v.8 no.4
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• pp.539-547
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• 2013

PURPOSE: This study examined the effects of exercise of diverse intensities on the expression of TNF-${\alpha}$(tumor necrosis factor-${\alpha}$) in the spinal cord in osteoarthritic rats. METHODS: Over a period of four weeks, the authors applied treadmill exercise programs of diverse intensities to Sprague-Dawley rats, to which intra-articular injection of monosodium iodoacetate(MIA, $3mg/50{\mu}l$, diluted in saline) was applied to the right knee joint to induce osteoarthritis. The four-week exercise program was not carried out with the control group(CG, n=10). Exercise programs of applicable intensities were applied to the low-intensity exercise group(LEG, n=10), moderate-intensity exercise group (MEG, n=10), and high-intensity exercise group(HEG, n=10) over the four weeks. Observations were made of expression of TNF-${\alpha}$ in the spinal cord in osteoarthritic rats using western blot analysis. RESULT: there were significant differences(p<.05) in the comparison of expression of TNF-${\alpha}$ between the four groups involved. The expression of TNF-${\alpha}$ in the spinal cord, the LEG and HEG had more elevated expression significantly than the CG(p<.05). But the MEG had reduced expression significantly than the CG(p<.05). CONCLUSION: These study results suggest that moderate-intensity exercise is effective in inhibition TNF-${\alpha}$ in the spinal cord. They also indicate that in prescribing exercise to treat osteoarthritic patients, exercise of moderate intensity is most suitable to patients' chronic pain, rather than low or high intensity.

• Microbiology and Biotechnology Letters
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• v.27 no.1
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• pp.28-34
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• 1999

Ganoderan (GAN), an immunomodulating ${\beta}$-glucan from mushroom Ganoderma lucidum, was evaluated for its ability to induce formation of nitric oxide (NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and transforming growth factor (TGF-${\beta}$) from rat Kupffer cell in vitro. Hepatic macrophages activated by GAN significantly elevated concentration of NO and TNF-${\alpha}$ in cultured medium, but not significantly elevated that of TGF-${\beta}$. GAN-activated Kupffer cells secrete 14.9${\mu}$M (p<0.01) of NO and 2619.5${\rho}$g/ml (p<0.01) of TNF-${\alpha}$after 36hr of incubation at 37$^{\circ}C$. The results revealed that GAN enhanced 4-fold production of NO and 19 fold formation of TNF-${\alpha}$ compared to the control. The proliferation of GAN-activated Kupffer cells was inhibited as compared with its negative control. Comparing the activity among glucans derived from microorganisms, highly branched zymosan, glucomannan from Saccharomyces cerevisiae, significantly increased TNF-${\alpha}$ and NO production. These results indicate that the ${\beta}$-glucan from G. lucidum activates rat Kupffer cell and secretes NO and TNF-${\alpha}$. It also suggest that rat Kupffer cell posses certain receptor for ${\beta}$-anomeric glucan.

• Proceedings of the Microbiological Society of Korea Conference
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• 2004.05a
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• pp.65-67
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• 2004

O-GlcNAcylation of p53 has been already identified and reported, but the function of O-GlcNAc on p53 has not been studied well. In this report, the general function of O-GlcNAc modification on p53 has been investigated using mouse fibroblast cell, L929. When streptozotocin (STZ), a non-competitive O-GlcNAcase inhibitor was treated to L929, O-GlcNAc modification level was dramatically increased on nucleocytoplasmic proteins, including p53. Because it has been already reported that $TNF\alpha$ induced the production of p53 in L929, $TNF\alpha$ was treated to obtain more p53. Approximately two times more amount of p53 was found from the cells treated STZ and $TNF\alpha$ simultaneously compared to the cell treated $TNF\alpha$ alone. The p53 increment in the presence of STZ was not caused by the induction of p53 gene expression. When new production of p53 induced by the $TNF\alpha$ was inhibited by the treatment of cycloheximide, O-GlcNAc modification decreased and phosphorylation increased on pre-existing p53 after $TNF\alpha$ treatment. But in the presence of STZ and $TNF\alpha$ at the same time, more O-GlcNAcylation occurred on p53, The level of ubiquitination on p53 was also reduced in the presence of STZ. Approximately three times less amount of Mdm2 bound to this hyperglycosylated p53. From this result it might be concluded that treatment of STZ to inhibit O-GlcNAcase increased O-GlcNAc modification level on p53 and the increment of O-GlcNAc modification stabilized p53 from ubiquitin proteolysis system.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.131-138
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• 2012

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor ${\alpha}$ (TNF${\alpha}$) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNF${\alpha}$ production in vitro and $in$ $vivo$, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNF${\alpha}$ mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP- activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNF${\alpha}$ production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The $in$ $vivo$ effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNF${\alpha}$ mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNF${\alpha}$ production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNF${\alpha}$ production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNF${\alpha}$ production by cilostazol.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.233-239
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• 2014

The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-${\alpha}$ levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to $17{\alpha}$-ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-${\alpha}$ along with hippocampal kynurenine/tryptophan ratio were determined in mature ovariectomized rats treated orally either by HP at three different doses 125, 250, and 500 mg/kg/day or by $17{\alpha}$-ethinylestradiol $30{\mu}g/kg/day$ for 30 days. Ovariectomized rats showed significant increase in immobility time in the forced swimming test. Along with elevation in serum and hippocampal TNF-${\alpha}$ and corticosterone levels associated with significant increase in hippocampal kynurenine/tryptophan ratio. Immobility time in the forced swimming test was decreased in rats treated by different doses of HP in a dose dependent manner and $17{\alpha}$-ethinylestradiol with no concomitant changes in the open field test. Only Rats treated with HP exhibited significant decrease in the elevated serum and hippocampal TNF-${\alpha}$ and corticosterone, which couldn't explain the associated insignificant effect on hippocampaus kynurenine/tryptophan ratio in comparison to ovariectomized untreated rats. It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-${\alpha}$ might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-${\alpha}$ and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.135-142
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• 2006

Objectives : On-Bi-Tang(OB) has been prescribed Chinese traditional medicine for the treatment of inflammatory disease such as chronic renal failure. In this study, we investigated the anti-inflammatory effect of OB extract in the BV2 murine microglial cells. Methods : After the water extract of OB was treated in BV2 cells, murine microglial line, the cell viability was measured by MTT assay. The production of nitric oxide (NO) and $TNF-{\alpha}$ was determined based on Griess reagent and enzyme linked immunosorbant assay (ELISA). mRNA expression of inducible nitric oxide synthase (iNOS) and $TNF-{\alpha}$ was analyzed by RT-PCR. Results : OB extract significantly inhibited the LPS-induced production of NO and TNF-a in BV2 cells. OB extract also suppressed the mRNA expression of iNOS and $TNF-{\alpha}$ in BV2 cells activated with LPS. Conclusion : These data suggests that OB extract may have the anti-inflammatory effect through the modulation of NO production and inflammatory cytokine such as $TNF-{\alpha}$.

• International Journal of Oral Biology
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• v.35 no.2
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• pp.43-49
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• 2010

Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-$\alpha$. The present study investigated the mechanisms involved in TNF-$\alpha$ production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-$\alpha$. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-$\alpha$ by E. faecalis. In addition, antioxidant treatment reduced TNF-$\alpha$ production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-$\alpha$ expression by RAW 264.7 cells. Furthermore, activation of NF-${\kappa}B$ and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-$\alpha$ in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-${\kappa}B$, and AP-1.

• Biomedical Science Letters
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• v.19 no.1
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• pp.1-8
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• 2013

Parkin is known to be a tumor suppressor protein. Previously, we determined that parkin expression restores susceptibility to TNF-${\alpha}$-induced death of HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. MMP-3 is a zinc-dependent protease recently reported to activate intracellular apoptotic signaling. In this study we examined the regulation of MMP-3 expression by parkin in TNF-${\alpha}$-treated HeLa cells. Furthermore, we investigated the signaling pathway involved in parkin-induced expression of MMP-3. We found that HeLa cells exhibit low levels of MMP-3 but is induced after introduction of the parkin gene into HeLa cells. Furthermore, MMP-3 expression increased further when parkin expressing cells were treated with TNF-${\alpha}$. Using chemical inhibitors of cell signaling pathways, we found that MEK-1 (PD98059), PI3K (LY294002), p38 MAPK (SB203580), and JNK inhibitors alleviated parkin-induced up-regulation of MMP-3. Finally, we show that TNF-${\alpha}$-induced cell death in parkin expressing cells is inhibited by using a MMP-3 inhibitor. These results suggest that parkin expression induces prolonged expression of MMP-3 via MEK-1, PI3K, MAPK, and JNK pathway in HeLa cells allowing the HeLa cells to become sensitive to TNF-${\alpha}$-induced cell death. These results implicate a role of MMP-3 in parkin-induced cell death in TNF-${\alpha}$ treated HeLa cells.

• BMB Reports
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• v.44 no.7
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• pp.462-467
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• 2011

Up-regulation of selected matrix metalloproteinases (MMPs) such as MMP-9 contributes to inflammatory processes during the development of various skin diseases, such as atopic dermatitis. In this study, we examined the effect of a cell-permeable superoxide dismutase (Tat-SOD) on TNF-${\alpha}$-induced MMP-9 expression in human keratinocyte cells (HaCaT). When Tat-SOD was added to the culture medium of HaCaT cells, it rapidly entered the cells in dose- and time-dependent manners. Tat-SOD decreased TNF-${\alpha}$-induced reactive oxygen species (ROS) generation. Tat-SOD also inhibited TNF-${\alpha}$-induced NF-${\kappa}B$ DNA binding activity. Treatment of HaCaT cells with Tat-SOD significantly inhibited TNF-${\alpha}$-induced mRNA and protein expression of MMP-9, as measured by RT-PCR and Western blot analysis. In addition, Tat-SOD suppressed TNF-${\alpha}$-induced gelatinolytic activity of MMP-9. Taken together, our results indicate that Tat-SOD can suppress TNF-${\alpha}$-induced MMP-9 expression via ROS-NF-${\kappa}B$-dependent mechanisms in keratinocytes, and therefore can be used as an immunomodulatory agent against inflammatory skin diseases related to oxidative stress.

• Journal of Oriental Neuropsychiatry
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• v.11 no.2
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• pp.11-21
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• 2000

Substance P(SP) can stimulate production of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) from astrocytes stimulated with lipopolysaccharide(LPS). The objective of the current study was to determine the effect of Taraxacum officinale(TO) on the production of TNF-${\alpha}$ from primary cultures of rat astrocytes. TO(100& 1000$\mu\textrm{g}$/ml) significantly inhibited the TNF-${\alpha}$ production by astrocytes stimulated with LPS and SP. Interleukin-1(IL-1) has been shown to elevate TNF-${\alpha}$ production from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-${\alpha}$ production from primary astrocytes by TO. Treatment of TO(100 and 1000$\mu\textrm{g}$/ml) to astrocytes stimulated with both LPS and substance P decreased IL-1 production significantly. Moreover, the production of TNF-${\alpha}$ by LPS and substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. These results suggest that TO may inhibit TNF-${\alpha}$ production by inhibiting IL-1 production and that TO has an antiinflammatory activity in the central nervous system.