• International Journal of Oral Biology
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• 제36권2호
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• pp.91-101
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• 2011

MspTL is the major surface protein of Treponema lecithinolyticum associated with periodontitis and endodontic infections. Our recent investigation revealed that MspTL induces proinflammatory cytokines and intercellular adhesion molecule 1 in THP-1 cells and periodontal ligament cells. In this study we conducted oligonucleotide microarray analysis to investigate the global transcriptional regulation in THP-1 cells stimulated with purified recombinant MspTL. MspTL upregulated the expression of 90 genes in THP-1 cells at least four fold, and the functions of these genes were categorized into adhesion, apoptosis/antiapoptosis, cell cycle/growth/differentiation, chemotaxis, cytoskeleton organization, immune response, molecular metabolism, proteolysis, signaling, and transcription. The majority of the modified genes are known to be NF-${\kappa}B$-responsive and interferon-stimulated genes (ISGs). The expression of 12 selected genes was confirmed by real-time RT-PCR. Because prostaglandin $E_2(PGE_2)$ is an important inflammatory mediator and Cox-2 was found to be induced by MspTL in the microarray analysis, we determined the level of $PGE_2$ in the culture supernatants of MspTL-treated cells and found that MspTL significantly increased $PGE_2$. Our results provide insight into the gene regulation of host cells in response to MspTL, and may contribute to the understanding of the molecular mechanism in periodontitis.

• YAKHAK HOEJI
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• 제52권5호
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• pp.402-406
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• 2008

Previously, we have shown that 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has an anti-inflammatory activity in a rat paw-edema model. In the present study, we investigated an inhibitory effect of FPP-3 on the tumor necrosis factor (TNF)-${\apha}$-induced inflammatory cytokine response in HT-29 human colon epithelial cells. Treatment with FPP-3 significantly prevented the TNF-${\apha}$-induced attachment of leukocytes to HT-29 colon epithelial cells, which is one of the pathologic hallmarks in colon inflammation. The effect of FPP-3 was markedly superior than that of 5-aminosalicylic acid (5-ASA), a commonly used drug for the treatment of inflammatory bowel disease (IBD). The pretreatment with FPP-3 inhibited TNF-${\apha}$- induced monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 mRNA expressions. In addition, FPP-3 significantly suppressed TNF-${\apha}$-induced nuclear factor (NF)-${\kappa}B$ transcription activity. These results demonstrate that FPP-3 modulates intestinal inflammation via suppressing the NF-${\kappa}B$ dependent expressions of MCP-1 and IL-8, and suggest that FPP-3 may be a valuable agent for the treatment of IBD.

• Journal of Physiology & Pathology in Korean Medicine
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• 제23권6호
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• pp.1320-1331
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• 2009

Oxidative stress and inflammation are important events in the development of chronic inflammatory diseases including arthritis, atherosclerosis, diabetes, hypertension. Cynomorium songaricum (CS) has been used as a traditional Korean herbal medicine, and it is currently used in traditional clinics to treat frequent urination, spermatorrhea, weakness of the sinews and constipation in the folk medicine. The aim of this study was to determine whether fractionated extracts of CS inhibit free radical generation such as DPPH radical, superoxide radical, nitric oxide and peroxynitrite, production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Our results indicated that the most superior extract which scavenged DPPH radical, reactive oxygen species (ROS) and RNS was CS ethyl acetate extract (CSEA). Moreover, CSEA significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-$\alpha$, IL-$1{\beta}$ and IL-6 formation in macrophages. Furthermore, CSEA treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$. These findings indicate that CSEA inhibits the production of pro-inflammatory mediators and cytokines via the suppression of ROS production and NF-${\kappa}B$ activation. Take together, these results indicate that CSEA has the potential for use as an natural anti-oxidant and an agent of anti-chronic inflammatory diseases.

• The Journal of Korean Obstetrics and Gynecology
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• 제24권4호
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• pp.31-49
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• 2011

Objectives: This study was performed to assess the protective effect of Polygonum multiflorum(PM) on UVB-irradiated HaCaT Keratinocytes damage. Methods: The protective effects of Polygonum multiflorum(PM) were determined by UVB-irradiated HaCaT assay. We assessed protective effects of Polygonum multiflorum(PM) on LDH release and nitrite production from HaCaT. COX-2, Bcl-2, Bax, $TNF{\alpha}$, c-jun, c-fos, NF-${\kappa}B$, iNOS, Bcl-xL gene expression were determined in HaCaT using real-time PCR method. Results: 1. PM inhibited LDH Release in UVB-irradiated HaCaT Keratinocytes. 2. PM inhibited Nitrite Production in UVB-irradiated HaCaT Keratinocytes. 3. PM suppressed the Gene Expression of COX-2 in UVB-irradiated HaCaT Keratinocytes. 4. PM increased the Gene Expression of Bcl-2 in UVB-irradiated HaCaT Keratinocytes. 5. PM didn't increase the Gene Expression of Bax in UVB-irradiated HaCaT Keratinocytes. 6. PM suppressed the Gene Expression of $TNF{\alpha}$ in UVB-irradiated HaCaT Keratinocytes. 7. PM suppressed the Gene Expression of c-jun in UVB-irradiated HaCaT Keratinocytes. 8. PM suppressed the Gene Expression of c-fos in UVB-irradiated HaCaT Keratinocytes. 9. PM suppressed the Gene Expression of NF-${\kappa}B$ in UVB-irradiated HaCaT Keratinocytes. 10. PM suppressed the Gene Expression of i-NOS in UVB-irradiated HaCaT Keratinocytes. 11. PM didn't increase the Gene Expression of Bcl-xL in UVB-irradiated HaCaT Keratinocytes Conclusions: In conclusion, these results suggest that PM inhibited the cell damage in UVB-irradiated HaCaT.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• 제30권1호
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• pp.29-42
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• 2017

Objectives : Atopic dermatitis accompanies with severe pruritus and collapse of skin barrier, inflammation. Maifanite could be used as an ointment for skin disease. However, there have been few studies about maifanite uses for atopic dermatitis. We report the anti-inflammatory and promoting skin recovery effects of ionized maifanite on damaged skin barrier with experimentally elicited atopic dermatitis. Methods : Nc/Nga mice were divided into 3 groups: control group(CON), atopic dermatitis elicited group(AE group), ionized maifanite treated group after atopic dermatitis elicitation(MT group). After 5% SDS was applied D. pteronyssinus crude extract also applied for 3 weeks to elicit atopic dermatitis-like skin disease. MT group was treated for 3 weeks with ionized maifanite. Ionized maifanite was applied once a day and voluntarily administrated. AE group and control group were treated with normal saline in the same way. Results : In MT group, skin lesions like eczema were more improved than AE group. p-ERK1/2 positive reaction was reduced in MT group. MMP-9 and substance P positive reaction at dermal papillae was also reduced in MT group. With skin angiogram, capillary vessel decreased in MT group. Also, IL-4 positive reaction cell and STAT-6 positive reaction cell reduced more in MT group than in AE group. $NF-{\kappa}B$ p65 positive reaction cell and iNOS positive reaction cell also declined more in MT group than in AE group. Conclusions : It is supposed that ionized maifanite has anti-inflammatory effects on NC/Nga mice's atopic dermatitis with suppressing IL-4 production and Th2 cell differentiation, and controlling $NF-{\kappa}B$ activation.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.380-385
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• 2012

Glucosamine (GS) is well known for the treatment of inflammation. However, the mechanism and efficacy of GS for skin inflammation are unclear. The aim of this study was to evaluate the effects and mechanism of GS in the mouse 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema model. TPA-induced ear edema was evoked in ICR or transglutaminase 2 (Tgase-2) (-/-) mice. GS was administered orally (10-100 mg/kg) or topically (0.5-2.0 w/v %) prior to TPA treatment. Orally administered GS at 10 mg/kg showed a 76 or 57% reduction in ear weight or myeloperoxidase, respectively, and a decreased expression of cyclooxygenase-2 (COX-2), NF-${\kappa}B$ and Tgase-2 in TPA-induced ear edema by western blot and immunohistochemistry. Role of Tgase-2 in TPA ear edema is examined using Tgase-2 (-/-) mice and TPA did not induce COX-2 expression in ear of Tgase-2 (-/-) mice. These observations suggested that Tgase-2 is involved in TPA-induced COX-2 expression in the inflamed ear of mice and antiinflammatory effects of glucosamine is mediated through suppression of Tgase-2 in TPA ear edema.

• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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• pp.47-54
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• 2019

Estrogen withdrawal in post-menopausal women leads to overactivation of osteoclasts, which contributes to the development of osteoporosis. Inflammatory cytokines are known as one of mechanisms of osteoclast activation after estrogen deficiency. SPA0355 is a thiourea derivative that has been investigated for its antioxidant and anti-inflammatory activities. However, its efficacy in bone resorption has not been previously investigated. The aim of this study was to investigate the impact of SPA0355 on the development of osteoporosis and to explore its mode of action. In vitro experiments showed that SPA0355 inhibited receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages. This effect appears to be independent of estrogen receptor activation as ICI 180,782 failed to abrogate its effects on osteoclasts. Further signaling studies revealed that SPA0355 suppressed activation of the MAPKs, Akt, and $NF-{\kappa}B$ pathways. SPA0355 also increased osteoblastic differentiation, as evidenced by its effects on alkaline phosphatase activity and mineralization nodule formation. Intraperitoneal administration of SPA0355 to ovariectomized mice prevented bone loss, as verified by three-dimensional images and bone morphometric parameters derived from ${\mu}CT$ analysis. Noticeably, SPA0355 did not show hepatotoxicity and nephrotoxicity and also had little effect on hematological parameters. Taken together, the results indicate that SPA0355 may protect against bone loss in ovariectomized mice by stimulation of osteoblast differentiation and by inhibition of osteoclast resorption. Therefore, SPA0355 is a safe and potential candidate for management of postmenopausal osteoporosis.

• Journal of the Korean Applied Science and Technology
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• 제35권4호
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• pp.1369-1378
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• 2018

The purpose of this study was to investigate the effect of skate skin collagen peptide (SCP) according to its molecular weight (<1,000 Da or >1,000 Da) which was divided using the ultrafilatration method. The 200 mg/kg collagen peptide was administrated to obesity-induced db/db mice for 8 weeks. As the results, in collagen peptide-treated groups, body weight gain was decreased, the plasma and hepatic concentration of reactive oxygen species decreased and oxidative stress was alleviated. In addition, SCP-treated group showed the significant reduction of the protein expressions of nuclear transcription factors($NF-{\kappa}B$), enzymes(COX2, iNOS), and inflammatory cytokine(IL-6) in hepatic tissue, compared with those of the obese control group. There was a slight difference depending on the molecular weight of collagen peptide, but overall it was not significant. Therefore, SCP effectively inhibited the obesity-induced inflammatory response through attenuation of oxidative stress in the liver.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.63-70
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• 2019

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

• Journal of Microbiology and Biotechnology
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• 제29권8호
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• pp.1193-1203
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• 2019

We investigated the protective effects of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) from Polysiphonia morrowii Harvey against hydrogen peroxide ($H_2O_2$)-induced apoptosis in Vero cells. BDB exhibited scavenging activity for DPPH, hydroxyl, and alkyl radicals. BDB also inhibited $H_2O_2$-induced lipid peroxidation, cell death, and apoptosis in Vero cells by inhibiting the production of ROS. To evaluate the molecular mechanisms of apoptosis inhibition, the expression of Bax/Bcl-xL and $NF-{\kappa}B$ was assessed by western blot assay. BDB significantly suppressed the cleavage of caspase-9 and PARP and reduced Bax levels in $H_2O_2$-induced Vero cells. Besides, BDB suppressed the phosphorylation of $NF-{\kappa}$B and the translocation of p65 in $H_2O_2$-induced cells. Furthermore, we evaluated the effect of BDB on ROS production, cell death, and lipid peroxidation in an $H_2O_2$-stimulated zebrafish embryo model. Taken together, these results indicated that ROS generation and cell death were significantly inhibited by BDB in zebrafish embryos, thereby proving that BDB exerts excellent antioxidant activity in vitro and in vivo.