• Toxicological Research
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• v.27 no.3
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• pp.167-172
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• 2011

We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) activates macrophage function. Analysis of the infiltration of macrophages into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages into the peritoneal cavity. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including IL-$1{\beta}$, TNF-${\alpha}$, and IL-6 in mouse peritoneal macrophages. GDB increased the expression of IL-$1{\beta}$, TNF-${\alpha}$, and IL-6. Cytokine induction by GDB was further confirmed by RT-PCR and ELISA in mouse macrophage cell line, RAW264.7 cells. Treatment of RAW264.7 cells with GDB produced strong induction of NF-${\kappa}B$ DNA binding and MAPK phosphorylation, markers for macrophage activation and important factors for cytokine gene expression. Collectively, this series of experiments indicates that GDB stimulates macrophage activation.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.369-376
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• 2008

In the present study, we investigated the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl) on irradiated rat lungs to determine its potential as a radioprotective agent. We found that early lung damage induced by irradiation was reduced by treatment with 40mg/kg of cyclo(L-phenylalanyl-L-prolyl) in the latent and early pneumonitis phases. Expression of $TNF-{\alpha}\;and\;TGF-{\beta}1$ at 2 and TGF-${\beta}1$ at 8 weeks post-irradiation was decreased in animals that received both radiation and cyclo(L-phenylalanyl-L-prolyl) compared with animals that received radiation alone. Evidence indicated that the proinflammatory cytokine TNF-${\alpha}$ and the fibrogenic cytokine TGF-${\beta}1$ likely play a role in the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl). However, besides TNF-${\alpha}$ and TGF-${\beta}1$ expressions, the precise mechanism by which cyclo(L-phenylalanyl-L-prolyl) ameliorates the induced radiation damage is not clear.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.861-869
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• 1998

Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

• Urogenital Tract Infection
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• v.13 no.3
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• pp.51-57
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• 2018

Purpose: The effects of Lactobacillus fermentation extract (LFE) on cystitis induced by Escherichia coli lipopolysaccharide (LPS) in the mouse bladder were investigated by pathological analyses and measurement of the levels of tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-18 (IL-18). Materials and Methods: LFE was administered orally ($5{\mu}g/L$) to mice for 10 days after which the study group (n=12) received transurethral injection of $5{\mu}g/L$ LPS. The bladder tissue was then harvested after 24 hours and subjected to hematoxylin and eosin staining. A semi-quantitative score was used to evaluate inflammation (bladder inflammation index, BII). $TNF-{\alpha}$ immunohistochemical staining and multiplex cytokine assays were also performed. $TNF-{\alpha}$ and IL-18 levels were determined. The results were compared with those of the control group (n=12). Results: The BII in the control and study groups was $2.7{\pm}0.5$ and $1.1{\pm}0.7$, respectively, with the control group scores differing significantly from the study group scores (p<0.001). $TNF-{\alpha}$ immunohistochemical staining results were similar. The $TNF-{\alpha}$ levels determined by the multiplex cytokine assay were $2.82{\pm}1.35pg/mg$ and $1.55{\pm}0.56pg/mg$ for the control and study groups, respectively, and the difference between these groups was statistically significant (p=0.007). Conclusions: Oral administration of LFE appears to have a preventive effect against the inflammatory responses and $TNF-{\alpha}$ expression induced by transurethral instillation of LPS in the mouse bladder. Further studies are required to determine the clinical application of this finding.

• The Korea Journal of Herbology
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• v.22 no.3
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• pp.93-99
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• 2007

Objective : The present study was carried out to investigate the effects of Folium Perillae (FP) on several cytokine production such as IL-1$\beta$, TNF-$\alpha$, IL-10 and TGF-$\beta$ to determine related mechanisma in Rats. Methods: So, we investigated the effects of FP on levels of several cytokines such as IL-l$\beta$, TNF-$\alpha$, IL-10 and TGF-$\beta$ in ischemic rats. Results: In this experiment, IL-10, an immune-modulatory cytckine, level was elevated by treatment with FP, but another regulatory cytokine, TGF-$\beta$1 level was not affected. On the other hand, levels of IL-l$\beta$ and TNF-$\alpha$, an inflammatory cytokines, were lowered by treatment with FP effectively. Conclusion : In conclusion, these results suggest that FP is useful to treat patient with disease related to cerebral ischemia, because FP can elevate IL-10 level, lower IL-l$\beta$ and TNF-$\alpha$ levels.

• 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.

• Advances in Traditional Medicine
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• v.2 no.1
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• pp.41-46
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• 2002

In our study, the several cytokines were determined in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Adamantiades-Behcets patients. Adamantiades-Behcets disease (ABD) is a systemic inflammatory disorder and might involve immune dysfunction. High levels of $TNF-\alpha,\;IL-1\beta$ and $IFN-{\gamma}$ indicate the activation of inflammatory reactions and immune system in ABD. Gami-Phedoc-San (GPS) is an Oriental herbal medication, which has been used in Korea for the treatment of ABD. GPS (1 mg/ ml) significantly inhibited the secretion of proinflammatory cytokines, $TNF-\alpha\;and\;IL-1\beta$, compared to absence of GPS (by $50.5{\pm}1.9%$ inhibition for $TNF-\alpha$ and $106.9{\pm}16.8%$ for $IL-1\beta$). GPS also inhibited the production of $IFN-\gamma$, immunoregulatory Th1 cytokine, by $78.4{\pm}2.8%$. The inhibitory effects of GPS on cytokine secretion showed dose-dependent manner, and the pre-treatment of 1 mg/ml GPS had better effects than immunosuppressive drug for treatment of ABD, cyclosporin A. Our results suggest that GPS treatment for ABD patients might have pharmacological activity of immune and inflammatory responses through the cytokine modulation.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.6
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• pp.315-322
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• 2005

In this study, the authors investigated whether death of vascular smooth muscle cell (VSMC) had a pathological pertinence. Conditioned media obtained from rat aorta smooth muscle cell (SMC) that were induced death by expressing FADD in the absence of tetracycline (FADD-SMC) triggered death of normal SMC. DNA fragmentation and caspase-3 activation were observed in dying SMC by conditioned media. FADD-SMC showed transcriptional activation of tumor necrosis factor $(TNF)-{\alpha}$. Conditioned medium contained $TNF-{\alpha}$, indicating secretion of the cytokine from dying FADD-SMC. It was investigated if secreted $TNF-{\alpha}$ was functional. Conditioned medium activated ERK and p38 MAPK pathways and induced MMP-9 expression, whereas depletion of the cytokine with its soluble receptor (sTNFR) remarkably inhibited induction of MMP-9 by conditioned medium. These findings suggest that $TNF-{\alpha}$ in conditioned medium seems to be active. Then, contribution of $TNF-{\alpha}$ on death-inducing activity of conditioned medium was examined. Depletion of $TNF-{\alpha}$ with soluble $TNF-{\alpha}$ receptor decreased the death activity of conditioned medium by 35%, suggesting that $TNF-{\alpha}$ play a partial role in the death activity. Boiling of medium almost completely abolished the death-inducing activity, suggesting that other heat labile death inducing proteins existed in conditioned medium. Taken together, these results indicate that SMC undergoing death could contribute to inflammation by expressing inflammatory cytokines and pathological complications by inducing death of neighboring cells.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.15-22
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• 2014

Aggregatibacter actinomycetemcomitans is an important pathogen in the development of localized aggressive periodontitis. Lipopolysaccharide (LPS) is a virulent factor of periodontal pathogens that contributes to alveolar bone loss and connective tissue degradation in periodontal disease. Our present study was designed to investigate the cytokine expression and signaling pathways regulated by A. actinomycetemcomitans LPS (Aa LPS). Cytokine gene expression profiling in RAW 264.7 cells was performed by microarray analyses. The cytokine mRNA and protein levels and related signaling pathways induced by Aa LPS were measured by RT-PCR, ELISA and western blotting. Microarray results showed that Aa LPS strongly induced the expression of NF-${\kappa}B$, NF-${\kappa}B$-related genes, inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in RAW 264.7 cells. NF-${\kappa}B$ inhibitor pretreatment significantly reduced the levels of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA and protein. In addition, the Aa LPS-induced TNF-${\alpha}$ and IL-$1{\beta}$ expression was inhibited by p38/JNK MAP kinase inhibitor pretreatment. These results show that Aa LPS stimulates TNF-${\alpha}$ and IL-$1{\beta}$ expression through NF-${\kappa}B$ and p38/JNK activation in RAW 264.7 cells, suggesting the essential role of this pathway in the pathogenesis of localized aggressive periodontitis.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.332-342
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• 2000

Background : The importance of pro-inflammatory cytokines, especially tumor necrosis factor $\alpha$ (INF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the activation of NF-${\kappa}B$. However, the relationship between pro-inflammatory cytokine expression and NF-${\kappa}B/I{\kappa}B$ pathway in lung epithelial cells is not clear. Methods : BEAS-2B, A549, Na-H157, NCI-H719 cells were stimulated with IL-$1{\beta}$ or TNF-$\alpha$ at various times, and then IL-8 and TNF-$\alpha$mRNA expressions were assayed by Northern blot analysis. IL-$1{\beta}$ or TNF-$\alpha$-induced NF-${\kappa}B$ activation was assessed by the nuclear translocation of p65 NF-${\kappa}B$ subunit. The degradation of $I{\kappa}B{\alpha}$ and $I{\kappa}B{\beta}$ by IL-$1{\beta}$ or TNF-$\alpha$stimulation was assayed by Western blot analysis. The phosphorylation of $I{\kappa}B{\alpha}$ was evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation. The basal level of IKK $\alpha$ expression was evaluated by Western blot analysis. Results: $I{\kappa}B{\alpha}$ and $I{\kappa}B{\alpha}$ was rapidly degraded after 5 minutes of incubation with IL-$1{\beta}$ or TNF-$\alpha$ in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-${\kappa}B{\alpha}$ and the induction of IL-8 and TNF-$\alpha$ mRNA expression were observed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in these cells. In contrast, neither the changes in NF-${\kappa}B/I{\kappa}B$ pathway nor IL-8 and TNF-$\alpha$mRNA expression was induced by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in NCI-H719 cells. IL-$1{\beta}$ and TNF-$\alpha$-induced $I{\kappa}B$ phosphorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKK$\alpha$ expression was not different between cell. Conclusion : NF-${\kappa}B/I{\kappa}B$ pathway plays an important role in the expression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-${\kappa}B/I{\kappa}B$ pathway in NCI-H719 cells sæms to be due to the defect in the intracellular signal transduction pathway upstream to IKK.