• BMB Reports
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• v.48 no.2
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• pp.109-114
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• 2015

The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.13-20
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• 2008

Background: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. Methods: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 ($PGE_2$), interleukin (IL)-2 and IFN-${\gamma}$ were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. Results: The CCE at $100{\mu}g/ml$ significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-${\gamma}$) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. Conclusion: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.

• Herbal Formula Science
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• v.19 no.2
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• pp.11-22
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• 2011

Objectives : Hwangyeonhaedok-tang(HHDT) has been traditionally used for various clinical symptoms associated with gastrointestinal disorder, cardiovascular diseases, and inflammation in the Oriental medicine. However, little is known for antioxidant and anti-inflammatory effects of HHDT on dextran-sulfate sodium(DSS)-induced colitis in mice. Methods : In this study, we investigated an antioxidant and anti-inflammatory effects of HHDT on DSS-induced colitis in mice. An experimental colitis was induced by daily treatment with 5% DSS. HHDT was orally administrated the various concentrations(25-100 mg/kg, body weight/day) for 7 days with one time per day. Results : HHDT reduced significantly clinical sign of DSS-induced colitis, including body weight loss, shorten colon length, disease activity index(DAI), and histological colon injury. HHDT also inhibited significantly serum NO and prostaglandine $E_2(PGE_2)$ productions in DSS-induced colitis mice. Furthermore, HDDT increased significantly an superoxide anion(SOD), catalase, and glutathione peroxidase(GPx) activity of the colon tissue in DSS-induced colitis mice. Conclusions : These results suggest that HHDT administration could reduce significantly the clinical signs and inflammatory mediators, and increase antioxidant activity in DSS-induced colitis model mice and is a good candidate for further evaluation as an effective anti-ulcerative agent.

• Herbal Formula Science
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• v.17 no.2
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• pp.85-98
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• 2009

The fruits of Schisandra chinensis and Prunus mume have been traditionally used in the Oriental countries as an astringent against diarrhea and abdominal pain, a protectant for liver disease, an antimicrobial, and a blood tonic. However, little is known about the extract of Schizandrae Fructus and Mume Fructus (SMF-Ex) on dextran-sulfate sodium (DSS)-induced colitis in mice. In this study, we investigated the protective effects of SMF-Ex on DSS-induced colitis in mice. An experimental colitis was induced by daily treatment with 5% DSS. SMF-Ex was orally administrated the single dose (80 mg/kg, body weight/day) for 7 days with one time per day. SMF-Ex reduced significantly clinical sign of DSS-induced colitis, including body weight loss, shorten colon length, increased disease activity index (DAI), and histological colon injury. SMF-Ex also inhibited significantly nitric oxide (NO) and prostaglandine $E_2$ ($PGE_2$) productions in DSS-induced colitis mice. Furthermore, SMF-Ex increased significantly an superoxide anion (SOD), catalase, and glutathione peroxidase (Gpx) activity of the colon tissue in DSS-induced colitis mice. These results suggest that SMF-Ex administration could reduce significantly the clinical signs and inflammatory mediators, and increase antioxidant activity in DSS-induced colitis model mice and is a good candidate for further evaluation as an effective anti-ulcerative agent.

• The korean journal of orthodontics
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• v.24 no.4 s.47
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• pp.871-883
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• 1994

This experiment was designed to study possible roles of $interleukin-1\beta$, interleukin-6 and tumor necrosis $factor-\alpha$ in bone remodeling by measuring their effects on $PGE_2,\; LTB_4$ and collagenase production when they were administered to human periodontal ligament fibroblasts. Human periodontal ligament fibroblasts were collected from first premolars extracted for orthodontic treatment. They were incubated in the environment of $37^{\circ}C,\;5\%\;Co^2,\;and\;100\%$ humidity. They were treated with $0.25\%$ trypsin-EDTA solution and centrifuged. PDL cells in the fifth to seventh passage were used for the experiment. Cells were seeded onto the culture dishes and when they were successfully attached, human recombinant $interleukin-1\beta$, interleukin-6, and tumor necrosis $factor-\alpha$ were administered, alone or in combination. They were incubated for 4, 8 and 24 hours and the levels of $PGE_2,\;LTB_4$ and collagenase released into the culture media were assessed by enzymeimmunoassay and collagenase activity assay. The conclusions are as follows: 1. $IL-1\beta\;and\;TNF-\alpha$ were very active in stimulating the production of $PGE_2$ and collagenase by human periodontal ligament fibroblasts, while IL-6 increased $LTB_4$ production. 2. $IL-1\beta$ significantly increased $PGE_2$, but $LTB_4$ Production was not increased. $IL-1\beta$ is thought to act mainly via the cyclooxygenase pathway of arachidonic acid metabolism. 3. IL-6 tended to inhibit $IL-1\beta$ in the production of $PGE_2$ and collagense whereas IL-6 and $TNF-\alpha$ showed auditive effect in the level of $PGE_2$. The above cytokines increased the release of at least one of $PGE_2,\;LTB_4$ and collagenase. It suggests that cytokines are involved in bone remodeling process by stimulating PDL fibroblasts to produce various bone-resorptive agents. The roles of cytokines in bone remodeling as a whole would need further study.

• Journal of the Korean Society of Food Science and Nutrition
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• v.14 no.3
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• pp.253-258
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• 1985

It was aimed to elucidate the underlying mechanism which is elevated the systemic arterial blood pressure by cadmium(Cd). By using the isolated vas deferens and tail artery from Cd-poisoned rats, it was undertaken to see whether the ${\alpha}-adrenoceptor$ activity and prostaglandins action on the twitch response to electrical stimulation were altered. It was discussed in relation with sympathetic nerve activity. The response to electrical stimulation in vas deferens from Cd-poisoned rats was much enhanced, and frequency 50(Freq.50) was significantly lowered, comparing to control. However, the response of rat tail artery was attenuated by Cd. Inhibitory action of clonidine on the twitch response of vas deferens to electrical stimulation was decreased by Cd-poisoning. However, the increase in response in the presence of methoxamine was not affected. The inhibitory action of prostaglandin $E_2$ on the twitch response in the vas deferens but not in the tail artery was abolished or rather inverted by Cd-poisoning. In the tail artery from Cd-poisoned rats, the maximum contraction to methoxamine or clonidine was significantly decreased, however, $ED_{50}$ of both agonists was not changed. These results suggest that in vas deferens the autoreceptor of presynaptic membrane is inhibited by Cd-poisoning, by which mechanism the sympathetic activity is being enhanced and this alteration may be causally related to the elevation of arterial pressure.

• Journal of Periodontal and Implant Science
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• v.26 no.3
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• pp.641-654
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• 1996

In infectious disease, invasion of host tissue by bacteria or their products frequently induces a wide variety of inflammatory and immunopathologic reaction. Evidence indicates that cytokines are involved in the initiation and progression of chronic inflammatory diseases, such as periodontitis. Interleukin-6, which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. Periodontal diseases are characterized by chronic inflammation of the periodontium with alveolar bone resoption. A principal driving force behind this response appears to lie in the immune system's response to bacteria. Many of the cell components which have been shown to function as virulence factors in gram-negative bacteria are associated with the bacterial surface. Of these, lipopolysaccharide has been characterized as one that mediates a number of biological activities which can lead to the destruction of host tissue. Non-steroidal antiinflammatory drug is used for reduce inflammation, and most of NSAIDs inhibit prostaglandine $E_2$ production, but it is shown that $PGE_2$ production is stimulated by IL-1 in recent study. So, the influence of other cytokines except $PGE_2$ on periodontium can not be avoided. Therefore, new antiinflammatory drug is needed. Rhizoma coptidis is used in oriental medicine for anti-inflammation and antiseptics. In this present study, we examined the IL-6 release in periodontal ligament cells treated with the lipopolysaccharide, and also the effect of rhizoma coptidis on cellular activity and IL-6 production of periodontal ligament cells. To evaluate the effect of rhizoma coptidis on cellular activity, the cells were seeded at a cell density of $1{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 1-6, 10-9 and 10-12 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 1 and 2 days, respectively. Then, MTT assay were carried out. To evaluate the effect of rhizoma coptidis on IL-6 production, the cells were seeded at a cell density of $1.5{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 10-9 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 3, 6, 12 and 24 hours. Then, amounts of IL-6 production is measured by IL-6 ELISA kit used. The results were as follows : 1. Rhizoma coptidisrbelow to ($10^{-6}g/ml$) significantly increaed cellular activity of periodontal ligament cells than control. 2. Rhizoma coptidist ($10^{-9}g/ml$) significantly increased cellular activity of LPS($5{\mu}g/ml$)-treated periodontal ligament cells than control. 3. LPS(5 and $10{\mu}g/ml$) significantly increased IL-6 production of periodontal ligament cells than control. 4. Rhizoma coptidis($10^{-9}g/ml$) decreased IL-6 production of LPS ($5{\mu}g/ml$)-treated periodontal.ligarnent cells than LPS only tested group. These findings suggest that stimulation of the IL-6 release of periodontal ligament cells by LPS may have a role in the progression of inflammation and alveolar bone resoption in periodontal disease, and that inhibition of the IL-6 release of cells and stimulation of cellular activity by rhizoma coptidis may help the periodontal regeneration.