• Herbal Formula Science
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• v.16 no.2
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• pp.101-114
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• 2008

Objective : The purpose of this study was to investigate the anti-inflammatory effects of Hwagae-san extract(HGSE) on the peritoneal macrophage. Methods : To evaluate anti-inflammatory effects of HGSE, We measured cytokines(interleukin-6; IL-6, interleukin-12; IL-12, tumor necrosis factor-${\alpha}$; TNF-${\alpha}$) and nitric oxide(NO) production in lipopolysaccharide(LPS)-induced macrophages. Furthermore, We examined molecular mechanism using western blot and also LPS-induced endotoxin shock. Results : 1. HGSE did not have any cytotoxic effect in the peritoneal macrophages. 2. HGSE reduced LPS-induced IL-6, TNF-${\alpha}$, IL-12 and NO production in peritoneal macrophages. 3. HGSE inhibited the activation of extracelluar signal-regulated kinase(ERK), C-Jun NH2-terminal kinase(JNK) but not of p38, degradation of IkB-${\alpha}$ in the LPS-stimulated peritoneal macrophages. 4. HGSE inhibited the production of TNF-$\alpha$, IL-6 and IL-12 in serum after LPS injection. Conclusion : These results suggest that HGSE may inhibit the production of TNF-${\alpha}$, IL-6, and IL-12 through inhibition of ERK and JNK activation, and that HGSE may be beneficial for inflammatory diseases.

• The Korean Journal of Food And Nutrition
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• v.27 no.1
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• pp.43-49
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• 2014

Panax ginseng C.A. Meyer has been used as a traditional medicinal ingredient and the ginseng flower-buds also proved to have good medicinal properties. In this study, in order to enhance immune activities of ginseng flower-bud, the ginseng flower-bud extract was being fermented by Bacillus subtilis KCTC 1022 (BS), Lactobacillus plantarum KCTC3 and Saccharomyces cerevisiae strain CHY1011 (SC). Mice were orally administered daily for two weeks at two different concentrations (100 and 200 mg/kg B.W.). Treatment samples were water extracts of ginseng flower-buds (FD), water extracts of fermented ginseng flower-buds (FM) and controls for saline solution. Cytokine production (IL-6, TNF-${\alpha}$) either stimulated with LPS or not stimulated with LPS was detected by the ELISA assay when using the cytokine kit. Cytokine was statistically increased at supplemented groups with LPS in both the 100 and the 200 mg/kg B.W. and treatment with FM significantly decreased the LPS-induced TNF-${\alpha}$ and IL-6 production more than the treatment with FD. The results of this study may suggest that supplementation with FM increases the immune function by regulating cytokine production capacity for activated macrophages.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.835-845
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• 1998

Background: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well known. Method: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistochemical stain at 1, 2, 7 day, 2, 4, 8, 12 week, respectively. We investigated the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ in lung tissue. Results: 1) The expression of IL-6 increased from 1 day after exposure to 8 weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1 $\beta$ was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF-$\alpha$ expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-$\beta$ was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. Conclusion: The results above suggests IL-6, TNF-$\alpha$ appear to be a early inflammatory response in silica induced lung fibrosis and TGF-$\beta$ play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF-$\alpha$ production will be a key role in modultion of silica-induced fibrosis.

• KSBB Journal
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• v.25 no.1
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• pp.11-17
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• 2010

Here, we evaluated the effect of thrombin on the interleukin-6 production induced by tumor-necrosis-factor-$\alpha$ in endothelial cells. It is well known that tumor-necrosis-factor-$\alpha$ mediates inflammatory responses by activation of nuclear factor-kappa-B in endothelial cells. Here, we showed that lower concentration of thrombin decreased the production of interleukin-6 induced by tumor-necrosis-factor-$\alpha$ and this inhibitory effect of thrombin on interleukin-6 production was mediated by interacting with protease-activated-receptor-1. In addition, phosphoinositide-3-kinase was also involved the anti-inflammatory responses by lower concentration of thrombin in endothelial cells. These results suggested that lower concentration of thrombin mediated anti-inflammatory responses by interacting with protease-activated-receptor-1 on the cell membrane and phosphoinositide-3-kinase in the cell. These findings will provide the important evidence in the development of new medicine for the treatment of severe sepsis and inflammatory diseases and good clue for understanding unknown mechanisms by which thrombin showed the pro-inflammatory or anti-inflammatory activities in endothelial cells.

• Journal of Periodontal and Implant Science
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• v.24 no.1
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• pp.155-164
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• 1994

치조골흡수는 만성치주질환의 전형적인 증상이다. 골흡수에 작용하는 여러 요인들 중에서도, 특히 최근에 들어서 몇몇 cytokine들에 대한 관심이 높아지고 있는데, interleukin-1(IL-1), tumor necrosis factor(TNF) 및 interleukin-6(IL-6) 등이 치주질환의 진행과정에서 중요한 치조골흡수요인으로 제안되고 있다. 본 연구의 목적은 신생쥐의 골조직 배양실험을 통해서 recombinant human $interleukin-1{\beta}$ ($rHuIL-1{\beta}$), recombinant human tumor necrosis $factor-{\alpha}$($rHuTNF-{\alpha}$) 및 recombinant human interleukin-6(rHuIL-6) 의 골흡수 유도효과를 알아보고, cyclooxygenase 억제제인 indomethacin과 recombinant murine $interferon-{\gamma}$($rMurIFN-{\gamma}$)가 이들 cytokine의 골흡수 유도능력에 미치는 영향을 알아봄으로써 이들 cytokine의 작용기구에 대해서 알아보고자 하는데 있다. 생후 1-2일된 쥐에게 $1{\mu}Ci^{45}CaCl_2$를 피하주사하고 4일 후에 쥐를 희생시켜 $^{45}Ca$ 로 표지된 두개골을 얻어 24시간 전배양 후, 각 cytokine ($rHuIL-1{\beta}$, $rHuTNF-{\alpha}$ 및 rHuIL-6)과 cytokine 및 첨가약제 (indomethacin 및 $rMurIFN-{\gamma}$)가 함유된 배지로 교환하여 48시간 배양한다. 골흡수 유도효과는 두개골에서 48시간의 배양 중 유리되는 $^{45}Ca$의 방사능 정도로 평가하였다. 본 연구를 통해 다음과 같은 결과를 얻었다. 1. $rHuIL-1{\beta}$ ($10^{-12}-10^{-9}M$) 및 $rHuTNF-{\alpha}$ ($10^{-10}-10^{-8}M$)는 농도변화에 따르는 골흡수 유도효과를 보였으나 , rHuIL-6 ($10^{-10}-10^{-8}M$)는 유의할 만한 효과를 보이지 않았다. 2. Indomethacin ($10^{-6}M$)은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의할 만한 억제효과를 나타내지 않았다. 3. $rMurIFN-{\gamma}$ (1000 U/ml) 은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의한 억제효과를 나타내었다. 본연구를 통해 치주질환 환자의 치주조직에서 검출되는 $IL-1{\beta}$ 및 $TNF-{\alpha}$가 치조골 흡수에 중요한 역할을 할 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.6
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• pp.319-325
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• 2002

The induction of interleukin-6 (IL-6) using combined proinflammatory agents $(LPS/IFN-{\gamma}\;or\;TNF-{\alpha}/IFN-{\gamma})$ was studied in relation to p38 mitogen-activated protein kinase (MAPK) and $NF-{\kappa}B$ transcriptional factor in primary neonatal cardiomyocytes. When added to cultures of cardiomyocytes, the combined agents $(LPS/IFN-[\gamma}\;or\;TNF-{\alpha}/IFN-{\gamma})$ had stimulatory effect on the production of IL-6 and the elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. SB203580 inhibited protein production and gene expression of IL-6 in a concentration-dependent manner. In this study, $IFN-{\gamma}$ enhancement of $TNF-{\alpha}-induced\;NF-{\kappa}B$ binding affinity as well as p38 MAP kinase activation was observed. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on $TNF-{\alpha}/IFN-{\gamma}\;or\;LPS/IFN-{\gamma}-induced\;NF-{\kappa}B$ activation. This study strongly suggests that these pathways about $TNF-{\alpha}/IFN-{\gamma}$ or $LPS/IFN-{\gamma}-activated$ IL-6 release can be primarily dissociated in primary neonatal cardiomyocytes.

• The korean journal of orthodontics
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• v.27 no.3 s.62
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• pp.503-513
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• 1997

This study was undertaken to investigate the effect of oxygen tension on the activity and function of the cells derived from human periodontal ligament by measuring cell activity, total protein synthesis, collagen synthesis, $IL-1{\beta},\;IL-6,\;TNF-{\alpha}$ Human periodontal ligament fibroblasts were collected from premolars extracted for orthodontic treatment and incubated in the environment of $37^{\circ}C,\;5\%\;CO_2,\100\%$ humidity. After the fifth to sixth passage they were used for the experiment. Gaspack system to which $0.2{\mu}m$ Millipore filter was attached was connected to mixed-gas tanks. The mixed gases were composed of $10\%\;O_2,\;5\%\;CO_2,\;85\%\;N_2$ in hyoxic group or $90\%\;O_2,\;5\%\;CO_2,\;5\%\;N_2$ in hyperoxic group and $5\%\;CO_2,\;95\%$ air for control. After incubation in $37^{\circ}C$ for 2, 4, 6 days, cell activity was determined by tetrazolium(MTT) assay and total protein synthesis was assayed using sulforhodamine B(SRB). And measurement of 4-hydroxyproline was performed to assess collagen synthesis md $IL-1{\beta},\;IL-6,\;and\;TNF-{\alpha}$ were measured by enzymeimmunoassay. The results were as follows. 1. The cell activity and total protein synthesis in hypoxic group were a little higher than or almost the same with those in control group. 2. In hyperoxic group, the cell activity was lower than that in control group and total protein synthesis was decreased. 3. Collagen synthesis was significantly decreased initially in both hypoxic and hyperoxic group and increased nearly to the level of control group as the duration of cell incubation was longer 4. As a result of enzymeimmunoassay, the amount of cytokines was $IL-6,\;TNF-{\alpha}\;and\;IL-1{\beta}$ in order. 5. $IL-6,\;TNF-{\alpha}\;and\;IL-1{\beta}$ were increased more rapidly in both hypoxic and hyperoxic group than in control group as the duration of cell incubation was longer. 6. There were more $IL-6\;and\;TNF-{\alpha}$ in hyperoxic group than in control group after 6 days, and there were more $IL-6\;and\;TNF-{\alpha}$ after 6 days than after 2 or 4 days in hyperoxic group. These results suggested that oxygen tension might modulate the production of extracellular matrix and cytokines in the cells derived from human periodontal ligament.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7831-7834
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• 2014

Objective: To explore the influence of different ways of blood transfusion on the expression levels of interleukins (IL) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) inperi-operative patients with esophageal cancer. Materials and Methods: A total of 80 patients with esophageal cancer who underwent radical operations were selected as study patients and randomly divided into an observation group (treated with autologous blood transfusion) and control group (with homologous blood transfusion). Changes of intra-operative indexes and peri-operative blood indexes, from hemoglobin (Hb) and hematocrit value (Hct), to levels of inflammatory factors like interleukins-6 (IL-6), IL-8, IL-10 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were compared. Results: Operations for patients in both groups were successfully conducted, and no significant differences in mean surgical duration and intra-operative hemorrhage volume, fluid infusion volume and blood transfusion volume were detected (p>0.05). Compared with values before surgery, Hb and Hct levels decreased significantly while white blood cell count (WBC) increased 1, 5 and 7 d after operation (p<0.05, p<0.01). In addition, WBC was apparently higher in observation group than in control group 5 and 7 d after operation (p<0.01). Compared with before surgery, in the observation group, levels of IL-6, IL-8 and IL-10 had no significant differences after operation (P>0.05), but TNF-${\alpha}$ level increased y (p<0.01), whereas in control group, IL-6 level had no significant difference (p>0.05), IL-8 level decreased obviously (p<0.05), IL-10 level increased markedly first and then decreased gradually as time passed but its level remained elevated (p<0.01), and TNF-${\alpha}$ level increased first and then decreased, and there was no significant difference 7 d after operation (p>0.05). Conclusions: Decreased IL-8 and increased IL-10 levels are two important reasons for immunosuppression after homologous blood transfusion, whereas autologous blood transfusion can alleviate this while increasing the TNF-${\alpha}$ level, which also has potential to improve anti-tumor immunity in the human body.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.41 no.4
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• pp.171-175
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• 2015

Objectives: The objective of this study was to identify salivary and serum concentrations of interleukin (IL)-8, IL-6, and tumor necrosis factor alpha ($TNF-{\alpha}$) in patients with oral lichen planus, oral leukoplakia, oral submucous fibrosis, and healthy controls. Materials and Methods: Patients selected included 54 oral lichen planus (41 to 65 years), 50 oral leukoplakia (42 to 65 years), 51 oral submucous fibrosis (41 to 65 years), and 50 healthy controls (42 to 65 years). Oral lichen planus, oral leukoplakia, and oral submucous fibrosis cases were diagnosed using histopathological analysis. Salivary and serum cytokine concentrations were measured using enzyme-linked immunoassay kits in all subjects. Results: The levels of serum and salivary $TNF-{\alpha}$, IL-6, and IL-8 were statistically significantly increased in oral leukoplakia, submucous fibrosis, and lichen planus in contrast to normal healthy subjects (P<0.05). Serum and salivary correlation analysis revealed strong and highly significant correlations for $TNF-{\alpha}$, IL-6, and IL-8 in all groups (r=0.72-0.82, P<0.05). Conclusion: Salivary and serum cytokines were also elevated when analyzed in oral precancerous lesions. Thus, salivary and serum IL-8, IL-6, and TNF-${\alpha}$ levels might act as diagnostic markers for detection of oral precancer.

• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.239-241
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• 2011

In this study, we investigated the kinetics of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6 and high mobility group box 1 (HMGB1) concentrations in a 48-h model of canine endotoxemia by lipopolysaccharide (LPS) injection. Four healthy beagles were slowly administered 1 mg/kg of LPS diluted in normal saline, while two others were administered normal saline as controls. Blood collection was performed at 0 h (baseline), 1 h and 3 h (for TNF-${\alpha}$), 6 h, 12 h, 24 h and 48 h of the experiment, and cytokine levels were determined using the sandwich ELISA method. Early increments of TNF-${\alpha}$ and IL-6 were observed (< 3 h), but HMGB1 levels increased the most at 12 h of the experiment and gradually decreased until 48 h. During the whole experiment, IL-6 and HMGB1 were sustained over 12 h of LPS injection, whereas TNF-${\alpha}$ decreased within 6 h of LPS injection. Taken together, canine HMGB1 levels increase relatively late (< 12 h) and sustained longer than TNF-${\alpha}$ and IL-6 in response to endotoxin. This is the first study to evaluate canine HMGB1 cytokine from endotoxemia in dogs.