• The Journal of Korean Medicine
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• v.24 no.1
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• pp.74-83
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Socheongryong-tang and Socheongryong-tang plus Sasam (Adenophorae Radix) on the mRNA expressions of Interleukin (IL)-6, IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) involved in the asthma model. Materials and Methods : In this study, BEAS-2B cell lines, human epithelial cells, were used. These cells were stimulated by tumor necrosis factor $(TNF)-{\alpha},{\;}IL-1{\beta}$ and histamine for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for the internal standard. After each 24 hours of the Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑 龍湯加沙蔘) treatment, total cellular RNAs were collected by applying RNAzol directly to the living cells. Then the transcriptional activities of IL-6, IL-8 and GM-CSF were measured by RT-PCR with electrophoresis. Results : In the Socheongryong-tang (小靑龍湯) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). In the Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). Conclusions : This study shows that Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) have dose-dependent inhibitory effects on the mRNA expressions of IL-6, IL-8 and GM-CSF in human epithelial cells, so these herbal medicines may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in the asthma model.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.199-210
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• 2003

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

• Radiation Oncology Journal
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• v.18 no.3
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• pp.205-213
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• 2000

Purpose : To determine the role of cytokines in the apoptosis of rat's liver following irradiation. Materials and Methods : Sprague-Dawley rats were irradiated to entire body with a single dose of 8 Gy. The rats were divided Into 5 groups according to the sacrlfice day after irradiation. The liver and blood after 1, 3, 5, 7, and 14 days irradiation were sampled for evaluation of mechanism of apoptosis and role of cytokine in relation to radiation-induced tissue damage. The study was composed of microscopic evaluation of liver tissue, in situ detection method for apoptosis, immunohistochemical stain of IL-1, IL-4, IL-6 and TNF, bioassay and radioimmunoassay of IL-6 in liver tissue and blood. Results : Radiation-induced liver damage was noted from first day of radiation, and most severe parenchymal damage associated with infiltration of chronic inflammatory cells was seen in the groups of 5 days after radiation. A number of apoptosis were observed 1 day after radiation on both light microscope and in situ method. Afterwards, the number of apoptosis was gradually diminished. On immunohistochemical study, IL-1 and TNF were expressed 1, 3 days after radiation, but not expressed after that. IL-4 was not expressed in the entire groups. IL-6 was expressed with strong positivity in 1, 3 days after radiation. Bioassay and RIA of IL-6 in liver tissue and blood showed the highest value in 1 day after radiation, and the value is diminished after then. Conclusion. Apoptosis seemed to be the important mechanism of radiation-induced liver damage, and is possibly induced by the release of cytokines, such as IL-1, IL-6, TNF in view the simultaneously increased appearance of pooptosis and cytokines.

• Korean Journal of Psychosomatic Medicine
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• v.10 no.2
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• pp.130-141
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• 2002

Objectives : Stress induces alteration of gastrointestinal function in which interleukin (IL) and hypothalamo-pituitary-axis are involved. Depression again is associated with functional gastrointestinal disorders (FGID) and interleukins. The author attempted to look into the role of interleukins in the FGID also the association of depression and stress in this context. Methods : Entered were 20 patients with FGID, diagnosed by Rome IT criteria and 20 healthy controls. Depression was measured by Hamilton Rating Scale for Depression (HAM-D), and stress of the last one year by Schedule of Recent Experience (SRE). Serum levels of IL-$1\beta$, IL-2, IL-6 were measured by Enzyme-linked Immunosorbent Assay and serum cortisol by Fluorescence Polarization Immunoassay. The results were as follows : Results: 1) Serum levels of IL-$1\beta$, IL-2 were significantly lower in the patients with FGID than those in the controls, but level of IL-6 did not differ between two groups. 2) The patient group showed significantly higher level of serum cortisol as well as higher degrees of depression and stress. 3) Positive correlation was noted between depression and serum cortisol, and between depression and IL-2. A trend of negative correlation was seen between depression IL-$1\beta$. Positive correlation was noted between SRE and IL-6 and IL-6 and serum cortisol. Conclusions : It was concluded that FGID might be related to depression and stress. Changes of the interleukins might be involved with elevated cortisol level.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.145-154
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Lonicerae Flos and Paeoniae Radix on the mRNA expression of IL-6, IL-16, and GM-CSF involved in the asthma model. Materials and Methods : In the study BEAS-2B cell lines, human epithelial cells were used. These cells were stimulated with tumor necrosis factor $(TNF)-\alpha$ for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for internal standard. After 24 hours of Lonicerae Flos, Paeoniae Radix, total cellular RNAs were collected treating RNA zol directly on the living cells. Then the transcriptional activities of IL-6, 16, GM-CSF were measured by RT- PCR with electrophoresis. Results : In the Lonicerae Flos study, the mRNA expression of IL-6, IL-16 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. In the Paeoniae Radix study, the mRNA expression of IL-6, IL-l6 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. Conclusion : This study shows that Lonicerae Flus and Paeuniae Radix have no inhibitory effects on the mRNA expression of IL-6, IL-16 and GM-CSF in BEAS-2B cell lines, human epithelial cells. Advanced studies are required to investigate the other mechanisms of inhibitory effect by Lonicerae Flus and Paeoniae Radix in the asthma model.

• Natural Product Sciences
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• v.12 no.2
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• pp.113-117
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• 2006

Quercitrin gallate was previously isolated from Persicaria lapathifolia (Polygonaceae) as an inhibitor of superoxide production. In the present study, quercitrin gallate was found to inhibit interleukin (IL)-6 production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an $IC_{50}$ value of $63\;{\mu}M$. Furthermore, quercitrin gallate attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6 promoter activity, indicating that the compound could down-regulate IL-6 expression at the transcription level. Since nuclear factor (NF)-kB has been shown to play a key role in LPS-inducible IL-6 expression, an effect of quercitrin gallate on LPS-induced NF-kB activation was further analyzed. Quercitrin gallate exhibited a dosedependent inhibitory effect on LPS-induced nuclear translocation of NF-kB without affecting inhibitory kB (IkB) degradation, and subsequently inhibited LPS-induced NF-kB transcriptional activity in macrophages RAW 264.7. Taken together, quercitrin gallate down-regulated LPS-induced IL-6 expression by inhibiting NF-kB activation, which could provide a pharmacological potential of the compound in IL-6-related immune and inflammatory diseases.

• Animal cells and systems
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• v.13 no.4
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• pp.391-397
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• 2009

The house dust mite (Dermatophagoides pteronissinus) is an important factor in triggering allergic diseases. The function of eosinophils, particularly in the production of cytokine or chemokine, is critical in understanding the pathogenesis of inflammatory diseases. In this study, we examined whether D. pteronissinus extract (DpE) induces the expression of monocyte chemotactic protein 1 (MCP-1)/CCL2, IL-8/CXCL8, and IL-6 that mediate in the infiltration and activation of immune cells and in its signaling mechanism in the human eosinophilic cell line, EoL-1. DpE increased the mRNA and protein expression of MCP-1, IL-8, and IL-6 in a time- and dose-dependent course in EoL-1 cells. In our experiments using signal-specific inhibitors, we found that the increased expression of MCP-1, IL-8, and IL-6 due to DpE is associated with Src family tyrosine kinase and protein kinase C $\delta$ (PKC $\delta$). In addition, the activation of extracellular signal-regulated kinase (ERK) is required for MCP-1 and IL-8 expression while p38 mitogen-activated protein kinase (MAPK) is involved in IL-6 expression. DpE induced the phosphorylation of ERK and p38 MAPK. PP2, an inhibitor of Src family tyrosine kinase, and rottlerin, an inhibitor of PKC $\delta$, blocked the activation of ERK and p38 MAPK. DpE induces the activation of ERK and p38 MAPK via Src family tyrosine kinase and PKC $\delta$ for MCP-1, IL-8, or IL-6 production. Increased cytokine release due to the house dust mite and the characterization of its signal transduction may be valuable in understanding the eosinophil-related pathogenic mechanism of inflammatory diseases.

• International Journal of Oral Biology
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• v.38 no.2
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• pp.73-80
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• 2013

Leptin is one of the adipocytokines produced from adipose tissue but its functions in periodontal tissue have not previously been investigated. In our current study, we examined the effects of leptin on the expression of interleukin (IL)-6 and IL-8 in periodontal ligament (PDL) cells and gingival fibroblasts. Leptin receptor expression was evaluated by RT-PCR and the production of cytokines was measured by ELISA. The phosphorylation of Akt and Erk1/2 was assessed by western blotting. mRNA of long and short form leptin receptors were detected in both PDL cells and gingival fibroblasts. Leptin was found to increase the production of IL-6 and IL-8 in both of these cell types, an effect which was not blocked by polymyxin B, an inhibitor of lipopolysaccharide (LPS). Leptin did not alter the production of IL-6 and IL-8 induced by LPS in PDL cells but increased Akt and Erk1/2 phosphorylation in these cells. These results suggest that leptin acts as an inducer of IL-6 and IL-8 in PDL cells and gingival fibroblasts.

• The Journal of Internal Korean Medicine
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• v.22 no.3
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• pp.367-377
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• 2001

Objectives: We aimed to identify. the effect of Jeongcheon-tang(定喘湯) and Cheongsangboha-tang(淸上補下湯) on the transcriptional activities of cytokine IL-4, IL-5, IL-6 and IL-10 involved in asthma model. Materials and Methods: RBL-2H3 cell lines were used. Cells were stimulated with calcium inophore($2{\mu}M$ : Sample group 1, $4{\mu}M$ : Sample group 2) for maximal gene expression. After 3rd treatment of samples and incubation(per 24hours), total cellular RNAs were collected using Trizol solution method. Then transcriptional activities of IL-4, IL-5, IL-6 and IL-10 were measured by RT-PCR with electrophoresis. Results: In IL-4 study, Jeongcheon-tang treated group showed 82.76%(Sample group 1) of transcriptional activities compared to the control group and Cheongsangboha-tang treated groups showed 85.77% (Sample group 1), 89.42% (Sample group 2) of transcriptional activities compared to the control groups. In IL-5 study, Jeongcheon-tang treated groups showed 88.24%(Sample group 1), 98.83%(Sample group 2) of transcriptional activities compared to the control groups and Cheongsangboha-tang treated group showed 73.66%(Sample group 2) of transcriptional activities compared to the control group. In IL-6 study, Jeongcheon-tang treated group showed 92.95%(Sample group 2) of transcriptional activities compared to the control group and Cheongsangboha-tang treated group showed n.40%(Sample group 2) of transcriptional activities compared to the control group. In IL-10 study, Jeongcheon-tang treated group showed 118.46% (Sample group 2) of transcriptional activities compared to the control group. Conclusions: This study shows that Jeongcheon-tang has the inhibitory effect on the transcription of IL-4, IL-5, IL-6 gene expression and the increasing effect on the transcription of IL-10 gene expression, and Cheongsangboha-tang has the inhibitory effect on the transcription of IL4, IL-5 and IL-6 gene expression in RBL-2H3 cell lines. Advanced studies are required to investigate the mechanisms of inhibition or increase by herbal medicine in asthma model.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.152-159
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• 2005

Background : Exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with increased airway inflammation, and the $NF-{\kappa}B$ is known to be an indicator of cellular activation and of inflammatory mediator production. This study was undertaken to investigate the change of cytokine characteristics and $NF-{\kappa}B$ activity in induced sputum of COPD patients during exacerbation and recovery of the disease. Methods : Sputum induction was performed in 37 patients with COPD during exacerbation and during recovery and in 15 healthy subjects. Cell counts, levels of IL-6, IL-8 and $TNF-{\alpha}$ in induced sputum and NF-kB activity in macrophage of induced sputum were measured. Results : Patients with COPD showed significantly increased levels of IL-6, IL-8 and $TNF-{\alpha}$(p<0.01) and increased $NF-{\kappa}B$ activity in induced sputum(p<0.05) as compared with control subjects. Level of IL-8 during exacerbation of COPD decreased significantly during recovery(p<0.05). $NF-{\kappa}B$ activity and levels of IL-6 and $TNF-{\alpha}$ tended to be decreased during recovery, but not siginificantly. Conclusion : Activation of $NF-{\kappa}B$ and increased levels of IL-6, IL-8 and $TNF-{\alpha}$ were thought to be associated with pathogenesis and exacerbations of COPD.