• Advances in Traditional Medicine
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• v.7 no.5
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• pp.518-526
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• 2008

Recently a major goal in asthma therapy is to reduce or prevent the inflammatory response of airway. Eosinophilic accumulation in the tissue is a prominent feature of allergic diseases including asthma. Production of chemokines by bronchial epithelial cells may contribute to the allergic inflammation by recruiting eosinophils. In this study we evaluated the inhibitory effect of Gamichungsangbohatang (GMCSBHT), used traditionally in treating asthma, on secretion of chemokines for eosinophils in human A549 epithelial cells. Chemokines such as eotaxin, RANTES, IL-8 were inhibited in a dose-dependent manner, but IL-16 showed no inhibition by GMCSBHT. These findings indicate that GMCSBHT might be a therapeutic value in treating asthma by suppression of chemokines secretion associated with local accumulation of eosinophils.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.289-299
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• 2004

Background : Although the pathophysiology of asthma has been reported, its mechanism has not been fully elucidated. The mast cell is an effector cells in allergic inflammation and secretes a number of chemokines. Chemokines are important for the recruitment of leukocytes to sites of infection, which is essential in host defense. Chemokines also contribute to the pathogenesis of several disorders such as asthma, chronic bronchitis, atopic dermatitis, allergic rhinitis, and rheumatoid arthritis. Objective : In this study, the aim was to identify the effect of Baekryunchihyo-tang(白蓮治哮湯) on expression of chemokines. This was examined by RT-PCR using the human mast cell line (HMC-l) Materials and Methods : HMC-l cells were used, which is known to secrete and express chemokines. In order to investigate the protective effect of Baekryunchihyo-tang(白蓮治哮湯), HMC-l cells were incubated with pretreatment of Baekryunchihyo-tang(白蓮治哮湯) for 24 hrs. RT-PCR analyses of chemokine genes of cells pretreated with Baekryunchihyo-tang(白蓮治哮湯) showed that expressions of IL-8, $MIP-l{\beta}$, and RANTES genes in these cells were lower and $MIP-l{\alpha}$ showed a similar pattern compared to the calcium ionophore-treated group. In addition, cell cytotoxicity concentration measurements were performed by MTT assay method. Results : After stimulation with 1 uM calcium ionophore A23178 for 2 hrs, IL-8, major one of CXC chemokines, was highly expressed, and expression of $MIP-l{\beta}$ and RANTES (CC chemokines) increased, while expression of $MIP-l{\alpha}$ did not change. The cell cytotoxicity of Baekryunchihyo-tang(白蓮治哮湯) with treatments at various concentrations and times was not observed, respectively. Conclusion : This study suggests that Baekryunchihyo-tang(白蓮治哮湯) has dose-dependent effects on mRNA expression of IL-8(CXC chemokines), $MIP-l{\beta}$ and RANTES(CC chemokines) in human mast cellline(HMC-l). So these herbal medicines may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanism of inhibition by herbal medicine in the asthma model. This study provides basic data on the possibility of the clinical treatment of Baekryunchihyo-tang(白蓮治哮湯) for allergic disorders.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.199-212
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• 2005

Objective : Airway inflammation is now regarded as a defining feature of asthma. The importance of eosinophits in the airway inflammation of asthma patients is widely recognized, and eosinophils mobilization in the respiratory epithelium is activated by chemoattractants and cytokines. This study was designed to examine the extent of the ability of Moutan Cortex Radicis to inhibit eosinophil chemotaxis of pulmonary epithelium after allergic stimulation. Material and Methods : Water extracts of Moutan Cortex Radicis and pulmonary epithelial cell lines A549(human type II-like epithelial cells) and human eosinophils were used. Cytotoxic effects of Moutan Cortex Radicis were estimated via MTS assay, and the effects of Moutan Cortex Radicis on chemokines from prestimulated A549 cells were estimated by sandwich ELISA and RT-PCR. Chemotaxis assay on prestimulated eosinophils treated with Moutan Cortex Radicis. was conducted Result : In this study we demonstrated that $TNF-{\alpha}$ and IL-4, $IL-1{\beta}$ induced the accumulation of chemokines' mRNA in the pulmonary epithelial cell lines A549 in a dose-dependent manner. Chemokines of eotaxin, ICAM-1, YCAM-1, IL-8, IL-16 were inhibited by Moutan Cortex Radicis in a dose dependent manner, but RANTES showed no inhibition due to Moutan Cortex Radicis. Eosinophil migration was inhibited at high concentrations of Moutan Cortex Radicis. Conculusion : These findings are indicative of supression of chemokines accomplished by Moutan Cortex Radicis treatment, demonstrating the potential therapeutic value of Moutan Cortex Radicis for treating diseases such as asthma.

• The Journal of Korean Oriental Chronic Disease
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• v.10 no.1
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• pp.1-20
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• 2005

Background and Objective: The importance of the presence of eosinophils in the airways of patients with fetal asthma has long been recognized, but the mechanism by which these cells are recruited and retained in the lung are only now being elucidated. Eotaxin is a potent and specific eosinophil chemoattractant that is mobilized in the respiratory epithelium after allergic stimulation. Material and Methods: We used water extracts of Liripois Tuber and pulmonary epithelial cell lines A549(human typeII-like epithelial cells) and human eosinophils. We estimated cytotoxic effects of Liripois Tuber via MTS assay, and estimated the effects of Liripois Tuber on chemokines from prestimulated A549 cells by sandwich ELISA and RT-PCR. We conducted chemotaxis assay on prestimulated eosinophils treated with Liripois Tuber. Result: In this study we demonstrated that $TNF-{\alpha}$, IL-4 and $IL-1{\beta}$ induced the accumulation of chemokines mRNA in the pulmonary epithelial cell lines A549 in dose-dependent manner. Chemokines were inhibited by Liripois Tuber in dose-dependent manner. The eosinophil migration was inhibited at high concentration of Liripois Tuber. Conculusion: These findings indicate that the supression of the expression of chemokines can be accomplished by Liripois Tuber treatment, raising the possibility that Liripois Tuber might be of therapeutic value in diseases such as asthma.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.129-142
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• 2005

Objective : Asthma is known as chronic airway inflammatory disease. This inflammation is conducted by various inflammatory cells including eosihophil. Chemotaxis is one way that circulating inflammatory cells invade a specific lesion. This study examines the degree to which Lonicerae Flos inhibits eosinophil chemotaxis at pulmonary epithelium after allergic stimulation. Material and Methods : Water extracts of Lonicerae Flos and pulmonary epithelial cell lines A549(human type II-like epithelial cells) and human eosinophils were used. Cytotoxic effects of Lonicerae Flos via MTS assay were estimated, as well as the effects of Lonicerae Flos on chemokines from prestimulated A549 cells by sandwich ELISA and RT-PCR. Chemotaxis assay was conducted on prestimulated eosinophils treated with Lonicerae Flos. Result : In this study $TNF-{\alpha}$ and IL-4, $IL-l{\beta}$ were seen to induced the accumulation of chemokines mRNA in the pulmonary epithelial cell lines A549 in a dose-dependent manner. Chemokines were inhibited by Liripois Tuber in a dose-dependent manner and especially, IL-8 and ICAM-l were inhibited considerably at $100\;{\mu}g/ml$ concentration of Lonicerae Flos. The eosinophil migration is inhibited in high concentration of Lonicerae Flos in a dose-dependent manner. Conclusion : These findings indicate that the supression of the expression of chemokines can be accomplished by Lonicerae Flos treatment, raising the possibility that Lonicerae Flos might be of therapeutic value in diseases such as asthma.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.18-25
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• 2007

Background: Although glucocorticoids (GCs) are effective in controlling asthma in the majority of patients, a subset of asthmatics fails to demonstrate a satisfactory response, even to systemic GC therapy. This population is referred to as being "steroid-resistant". The actual mechanism underlying steroid resistance in asthma remains to be elucidated. Methods: We have investigated how dexamethasone (DEX) regulates asthmatic phenotypes in a murine model of asthma, in which mice received i.p. immunization twice, followed by two bronchoprovocations with aerosolized OVA with a one-week interval, which we have recently described. Results: Pretreatment with DEX resulted in an inhibition of NF-${\kappa}B$ activation in asthmatic lungs, and also inhibited bronchoalveolar lavage (BAL) levels of NF-${\kappa}B$-dependent cytokines such as TNF-${\alpha}$ and CC chemokines [eotaxin and monocyte chemotactic protein (MCP)-1]. DEX was effective in suppressing airway hyperresponsiveness (AHR) at 10 h, Th2-dependent asthmatic phenotypes such as airway eosinophilia, BAL levels of Th2 cytokines (IL-5 and IL-13), and mucin production. However, DEX failed to suppress BAL levels of CXC chemokines [macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC)] and airway neutrophilia. Conclusion: Airway neutrophilia is among the phenomena observed in patients with severe GC-resistant asthma. This study will provide insight into the molecular basis for airway neutrophila seen in steroid-resistant asthma. Further studies are required to delineate the underlying mechanism of CXC chemokine expression in asthma.

• Biomedical Science Letters
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• v.17 no.1
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• pp.89-93
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• 2011

Asthma is an inflammatory airway disease and is characterized by the releases of inflammatory mediators including chemokines. They are mainly associated with the recruitment, activation and dysregulation of specific inflammatory cells, especially neutrophils in neutrophilic asthma. CC chemokines bind to CC chemokine receptors (CCRs) in the surface of their target cells. The aims of this study are to examine the CCR expression in neutrophils of bronchoalveolar lavage fluid (BALF) of asthmatic patients and to determine the alternation of migration and apoptosis of neutrophils by the BALF. We demonstrate that CCR3 strongly expresses in BALF neutrophils of asthmatic patients as compared to other CCRs and increases during apoptosis of the BALF neutrophils. The migration of asthmatic blood neutrophils increases in response to asthmatic BALF as compared to BALF of normal volunteer. In addition, asthmatic BALF includes the higher levels of IL-8 protein than normal BALF and it has no effect on apoptosis of asthmatic blood neutrophils. Taken together, our results indicate that CCR3 expression may be associated with unknown function of asthmatic BALF neutrophils and BALF may be involved in the recruitment of neutrophils into the airway, but not in the neutrophils apoptosis.

• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.280-286
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• 2001

Epigallocathechin-3-gallate (EGCG), the main polyphenol component in green tea, inhibits angiogenesis, urokinase, and matalloproteinases, and EGCG also has the antioxidative property. Recent reports proposed that EGCG may modulate the immune response on allergy or asthma. Human nasal mucosal fibroblasts are a rich source of cytokines, inflammatory mediators, and chemokines. Chemokines are important for the recruitment of leukocytes to sites of infection, which is essential in host defense. The objective of this study was to investigate the effect of EGCG on the expression of the chemokines such as RANTES (regulated upon activation, normal T cell expressed and presumably secreted), eotaxin, and interleukin-8 (IL-8) in human nasal mucosal fibroblasts after stimulation with cytokines like IL-4, tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $interferon-{\gamma}\;(IFN-{\gamma})$. To detect the expression of chemokine genes, RT-PCR was performed. Expressions of RANTES, eotaxin, and IL-8 mRNA stimulated with IL-4 and $TNF-{\alpha}$ were increased, respectively, while the expression of those genes incubated with $IFN-{\gamma}$ was similar pattern compared to control group. Analyses of chemokine genes of cells pretreated with EGCG showed that the expressions of eotaxin, and IL-8 genes stimulated $IFN-{\gamma}$ were higher compared with those not pretreated with EGCG.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.208-220
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• 2006

Objective: Eosinophils are typically characterized by a bilobar nucleus with highly condensed chromatin and cytoplasm containing two major types of granules, specific and primary granules, and lipid bodies. The role of inflammation in asthma and other allergic diseases of the airways is widely appreciated, and airway inflammation is now included as a defining feature of asthma. The importance of the presence of eosinophils in the airways of patients with fetal asthma has long been recognized, but the mechanism by which these cells are recruited and retained in the lungs are only now being elucidated. Eotaxin is a potent and specific eosinophil chemoattractant that is mobilized in the respiratory epithelium after allergic stimulation. Methods : Water extracts of Armeniacae Amarum Semen(AAS) and pulmonary epithelial cell lines A549(alveolar typeII epithelial cells) and human eosinophils were used. Cytotoxic effects of AAS and MIS assay were estimated, as well as the effects of AAS on chemokines from prestimulated A549 cells by sandwich ELISA and RI-PCR. Chemotaxis assay was conducted on prestimulated eosinophils treated with AAS. Results : In this study it is demonstrated that $TGF-{\alpha}$, IL-4 and $IL-1{\beta}$ induced the accumulation of chemokine mRNAs in the alveolar epithelial cell lines A549 in dose-dependent manner. Eotaxin and IL-8 were inhibited by AAS in dose-dependent manner(p<0.05). Eosinophil migration was inhibited at high concentrations of AAS(p<0.05). Conculusions : These findings are indicative of suppression of eotaxin and IL-8, and suggest that this is accomplished through AAS treatment. This raises the possibility that AAS is of therapeutic value in diseases such as asthma.

• The Journal of Internal Korean Medicine
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• v.27 no.2
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• pp.521-532
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• 2006

Backgrounds and Objectives: A major goat in asthma therapy isto reduce or prevent the inflammatory response associated with bronchial hyperresponsiveness, reversible airway obstruction and airway remodelling. Many studies have shown that eosinophilic infiltration is a prominent feathure in the pathophysiology of asthma. The importance of the Presence of eosinophils in the airways of asthmatics has long been recognized, but the mechanism by which these cells are recruited and retained in the lung are only now being elucidated Production of chemotactic cytokines by bronchial epithelial cells may contribute to the local accumulation of eosinophils in Patients with bronchial asthma. This study was designed to investigate the inhibitory effect of extraction of herbal dicoction, Gamichungsangbohatang(GMCSBHT) on eosinophil chemotactic cytokines. Material and Methods:We used water and 70% ethanol extracts of GMCSBHT and pulmonary epithelial cell lines A549(human type II -like epithelial cells). We estimated cytotoxic effects of GMCSBHT, and estimated the effects of water and 70% ethanol extracts of GMCSBHT on chemokines from prestimulated A549 cells by sandwich ELISA. Results: Chemokines of eotaxin, IL-8 were inhibited by GMCSBHT in dose-dependent manner. And ethanol extract of GMCSBHT has more inhibitory effects on eotaxin, IL-8 than hot water extract. Conculusions: These findings indicate that the supression of the expression of chemokines can be accomplished by GMCSBHT treatment, so GMCSBHT may inhibit the iuflammatory process by eosinophils in asthma.