• Advances in Traditional Medicine
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• v.5 no.1
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• pp.69-74
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• 2005

'SecSec' has been used for the purpose of prevention and treatment of throat diseases such as sore throat, cough, bronchial asthma and allergic asthma in Korea. However, its effect in experimental models remains unknown. To investigate the biological effect of SecSec, we examined cytotoxicity and secretion of inflammatory cytokines on human leukemic mast cell line, HMC-1, stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. SecSec by itself had no cytotoxicity on HMC-1. When SecSec (1 mg/ml) was added, the secretion of tumor necrosis factor-alpha $(TNF-{\alpha})$, interleukin (IL)-6, and granulocyte macrophage-colony stimulating factor (GM-CSF) was significantly inhibited about 47.20%, 25.55%, and 46.43%, respectively on PMA plus A23187-stimulated HMC-1 cells. But SecSec did not inhibit IL-8 secretion. These findings may help understanding the mechanism of action of this medicine leading to control activated mast cells on allergic inflammatory condition like asthma.

• Natural Product Sciences
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• v.13 no.4
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• pp.337-341
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• 2007

In this report, we investigated the effect of aqueous extract of vinegar treated small black soybean (Glycine max Merr.) (Leguminosae) (VSBS) on mast cell-mediated allergic reaction and pro-inflammatory cytokine secretion. VSBS inhibited compound 48/80-induced systemic reactions. VSBS attenuated immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis. In addition, VSBS decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated secretion of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6 and interleukin (IL)-8 in human mast cells. Our findings provide evidence that VSBS inhibits mast cell-derived allergic reactions.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.52-66
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• 2001

Background : NF-${\kappa}B$ is the most important transcriptional factor in IL-8 gene expression. Triptolide is a new compound that recently has been shown to inhibit NF-${\kappa}B$ activation. The purpose of this study is to investigate how triptolide inhibits NF-${\kappa}B$-dependent IL-8 gene transcription in lung epithelial cells and to pilot the potential for the clinical application of triptolide in inflammatory lung diseases. Methods : A549 cells were used and triptolide was provided from Pharmagenesis Company (Palo Alto, CA). In order to examine NF-${\kappa}B$-dependent IL-8 transcriptional activity, we established stable A549 IL-8-NF-${\kappa}B$-luc. cells and performed luciferase assays. IL-8 gene expression was measured by RT-PCR and ELISA. A Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation and an electromobility shift assay was done to analyze NF-${\kappa}B$ DNA binding. p65 specific transactivation was analyzed by a cotransfection study using a Gal4-p65 fusion protein expression system. To investigate the involvement of transcriptional coactivators, we perfomed a transfection study with CBP and SRC-1 expression vectors. Results : We observed that triptolide significantly suppresses NF-${\kappa}B$-dependent IL-8 transcriptional activity induced by IL-$1{\beta}$ and PMA. RT-PCR showed that triptolide represses both IL-$1{\beta}$ and PMA-induced IL-8 mRNA expression and ELISA confirmed this triptolide-mediated IL-8 suppression at the protein level. However, triptolide did not affect $I{\kappa}B{\alpha}$ degradation and NF-$_{\kappa}B$ DNA binding. In a p65-specific transactivation study, triptolide significantly suppressed Gal4-p65T Al and Gal4-p65T A2 activity suggesting that triptolide inhibits NF-${\kappa}B$ activation by inhibiting p65 transactivation. However, this triptolide-mediated inhibition of p65 transactivation was not rescued by the overexpression of CBP or SRC-1, thereby excluding the role of transcriptional coactivators. Conclusions : Triptolide is a new compound that inhibits NF-${\kappa}B$-dependent IL-8 transcriptional activation by inhibiting p65 transactivation, but not by an $I{\kappa}B{\alpha}$-dependent mechanism. This suggests that triptolide may have a therapeutic potential for inflammatory lung diseases.

• BMB Reports
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• v.42 no.5
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• pp.265-270
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• 2009

Due to their multiple biological activities, flavonoids have gained attention as potentially useful therapeutics for a variety of diseases including cancer, cardiovascular diseases, and autoimmune diseases. In this study, we demonstrated that several flavonoids, including kaempferol, quercetin, fisetin, and chrysin block TNF-$\alpha$ induced IL-8 promoter activation and gene expression in HEK 293 cells. In addition, phosphorylation and degradation of $I{\kappa}B{\alpha}$ and translocation of NF-${\kappa}B$ p65 were inhibited by these flavonoids in TNF-$\alpha$-stimulated HEK 293 cells. Furthermore, generation of reactive oxygen species (ROS) in response to TNF-$\alpha$ was reduced by the flavonoids. Moreover, although pretreatment with fisetin, quercetin, or chrysin decreased cell viability, kaempferol did not. Taken together, these findings suggest that kaempferol would be useful for the treatment of TNF-$\alpha$-induced 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.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.703-712
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• 1995

Background: Peripheral blood monocytes are important immune effector cells that play a fundamental role in cellular immunity. In addition to their antigen-presenting and phagocytic activities, monocytes/macrophage produce a vast array of regulatory and chemotactic cytokines. Interleukin-8(IL-8), a potent neutrophil-activating and chemotactic peptide, is produced in large quantities by mononuclear phagocytes and may be an important mediator of local and systemic inflammation. Overexpression by IL-8 of such inflammation may be an important step of tissue injury frequently seen in inflammatory reaction. So it could be hypothesized that the agents which block the production of IL-8 can decrease the inflammatory reaction and tissue injury. To evaluate this, we described the effect of Dexamethasone, $PGE_2$, Indomethacin and Interferon-$\gamma$(IFN-$\gamma$) on IL-8 mRNA and protein expression from LPS-stimulated human peripheral blood monocytes(PBMC). Method: PBMC was isolated from healthy volunteers. To evaluate the effect of Dexamethasone, $PGE_2$ & Indomethacin, these drug were treated for 1 hour before and after LPS stimulation and IFN-$\gamma$ was only treated I hour before the LPS stimulation. Northern blot analysis for IL-8 mRNA and ELISA for immunoreactive IL-8 protein in culture supernatant were performed. We repeated above experiment three times for Northern blot analysis and two times for ELISA and got the same result. Results: 1) Pre- and post-treatment of Dexamethasone suppressed both the LPS stimulated IL-8 mRNA expression and IL-8 protein release in PBMC. 2) IFN-$\gamma$ pre-treatment suppressed the IL-8 mRNA expression and IL-8 protein release in unstimulated cells. 3) In LPS stimulated cells, IFN-$\gamma$ suppressed the IL-8 mRNA expression but IL-8 protein release suppression was not observed. 4) $PGE_2$ and Indomethacin exert no effect on the LPS-stimulated IL-8 mRNA and protein expression in concentration used in this experiment ($PGE_2;10^{-6}M$, Indomethacin; $10{\mu}M$). Conclusion: One of the mechanism of antiinflammatory action of Dexamethasone can be explained by the suppressing effect of IL-8 production in some extent and by this antiinflammatory effect, dexamethasone can be used to suppress local and systemic inflammation mediated by IL-8.

• 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.

• Archives of Pharmacal Research
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• v.20 no.2
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• pp.176-179
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• 1997

Purine nucleosides were chlorinated by the reaction of acyl chloride in DMF with MCPBA under mild conditions with moderate yields. And, satisfactory method for the synthesis of ribonucleoside-$3^{I},5^{I}$-cyclic phosphates and its characterization by$^{1}H$ and $^{13}C$ nmr spectroscopy is described.

• Clinical and Experimental Pediatrics
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• v.50 no.3
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• pp.248-254
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• 2007

Purpose : Inflammation plays a major role in the pathogenesis of RDS and BPD in the immature lung. We investigated the possible role of IL-10 and IL-12 in the cord blood of preterm newborns with RDS or BPD. Methods : Forty preterm newborns whose mothers received antenatal care at Ewha Womans University Mokdong Hospital between January 2003 to June 2005, and agreed to testing their cord blood samples were enrolled. The gestational ages were below 34 weeks. Cord blood level of IL-10 and IL-12 were determined by ELISA. We separated the patients into 2 groups (RDS group and non-RDS group, BPD group and non-BPD group) and compared the cytokine levels and clinical records of the groups. Results : Cord blood IL-10 level showed a significant inverse correlation with gestational age and birth weight (P=0.001, P=0.005). Preterm infants with RDS showed higher IL-10 level (1.0 vs 0.1 pg/mL; P=0.001) in the cord blood than those without RDS. The differences remained statistically significant after correction for the effect of gestational age between both preterm groups. Despite similar cord blood IL-10 levels, preterm infants with BPD showed no significant difference with those without BPD. Conclusion : Cord blood IL-10 levels are increased in preterm infants which may be due to the immuno-suppression occurring during pregnancy and to fetal immaturity because these levels are inversely correlated with the gestational age. So, Cord blood IL-10 level can be used as the predictor of RDS.

• Proceedings of the Korean Society of Life Science Conference
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• 2005.09a
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• pp.54-54
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• 2005