• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.12-28
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• 2001

Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

• Clinical and Experimental Pediatrics
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• v.46 no.5
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• pp.495-499
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• 2003

Purpose : Eosinophil is one of the important inflammatory cell involved in the airway inflammation in childhood asthma. It has been demonstrated that markers of eosinophil activation, including eosinophil cationic protein or eosinophil protein X(EPX), are increased in childhood asthma. Furthermore, they are related to disease activity and are assumed to be helpful in monitoring the treatment effect as urinary EPX(U-EPX) can be obtained easily and in a noninvasive way in children of all ages. Methods : Twenty-five children(22 male and three female) aged $11.87{\pm}3.82$ years with stable asthma were challenged with methacholine and urine was collected from each child during the following periods; before methacholine challenge test(MCT); 0-3 hr after the end of MCT; 4-7 hr after the end of MCT; and 8-24 hr after the end of MCT. Bronchial reactivity was determined by using Dosimeter( Jeager, Germany) with serially diluted methacholine from 0.05 to 25.0 mg. The $FEV_1$ less than 80% of baseline value were classified into positive MCT. U-EPX was measured with a sensitive and specific radioimmunoassay(Pharmacia & Upjohn AB, Uppsala, Sweden). Results were expressed as ${\mu}gEPX/mmol$ creatinine. Results : An early airway response after MCT was associated with an increase of U-EPX excretion for 0-3 hr after methacholine inhalation in comparison with beseline values. Most subjects showed a small increase in U-EPX excretion during late asthmatic response for 4-7 hr, which then decreased to normal level in 8-24 hr. Also, a tendency for a higher increase of U-EPX was associated with a lower threshold of methacholine challenge and a longer duration of asthma. Conclusion : Measurement of EPX in urine is a noninvasive and easy method to assess the severity of airway inflammation in asthmatic children. It may be a helpful index of the events underlying the airway inflammatory responses during nonspecific bronchial challenge, and in monitoring asthma management.

• Tuberculosis and Respiratory Diseases
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• v.80 no.3
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• pp.247-254
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• 2017

Background: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. Methods: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. Results: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. Conclusion: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

• Tuberculosis and Respiratory Diseases
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• v.65 no.5
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• pp.405-409
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• 2008

Churg-Strauss syndrome is a rare form of systemic necrotizing vasculitis that occurs exclusively in patients with asthma, and is associated with blood and tissue eosinophilia. The classic pathology findings in the lung include a combination of eosinophilic pneumonia, granulomatous inflammation and necrotizing vasculitis. However, there are few reports of tracheobronchial mucosal lesions in Churg-Strauss syndrome. We report a case of Churg-Strauss syndrome with multiple tracheobronchial mucosal lesions in a 33-year-old man with a history of bronchial asthma and allergic rhinitis. He had been diagnosed with community acquired pneumonia at another hospital and was treated with antibiotics. However, the chest radiographic findings were aggravated and showed multifocal consolidations in the whole lung fields. He was transferred to the Asan Medical Center. Fiberoptic bronchoscopy revealed multiple nodular mucosal lesions of the trachea and bronchi. The histopathology of the mucosal lesions revealed necrotizing bronchial inflammation with eosinophilic infiltration. Video Assisted Thoracic Surgery was performed. The wedge resected lung tissue revealed chronic eosinophilic pneumonia that was consistent with Churg-Strauss syndrome. Methylprednisolone (1 mg/kg q 8 hr) was prescribed and his symptoms resolved gradually. The chest radiographic findings improved significantly, and a follow-up fiberoptic bronchoscopy performed eight days later showed that the tracheobronchial mucosal lesions had resolved. The patient was prescribed oral prednisolone for 20 months after discharge. Currently, the patient is not taking steroids and is being followed up.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.260-273
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• 2004

Backgrounds : In recent years, asthma has become recognized as a chronic inflammatory disease associated pathologically with airway epithelial inflammation and airway remodeling. Objectives : To evaluate the different effects of Hirudo depending upon pharmaceutical manufactures on the expression and the activities of IL-6 and GM-CSF in airway epithelial cells, samples of Hirudo(水蛭), Hirudo toasted with Talcum(水蛭滑石炒) and Hirudo toasted with Ephedrae Herba(水蛭麻黃炒) were tested. Methods : After inducing enhanced messenger RNA(mRNA) expression and secretion of each cytokine by tumor necrosis factor-alpha(10 ng/ml) treatment, cultured human bronchial epithelial cell line BEAS-2B was added to each sample$(l,\;10,\;100\;&\;1000\;{\mu}g/ml)$. Subsequently, DNA activities were analyzed. Specifically mRNA expression and culture supernatants(protein levels) of IL-6 and GM-CSF from BEAS-2B cells, were analyzed using luciferase reporter gene assay, reverse transcription-polymerase chain reaction(RT-PCR) analysis and enzyme-linked immunosorbent assay. Results : Hirudo toasted with Ephedrae Herba(水蛭麻黃炒) and Hirudo(水蛭) inhibited IL-6 activities in BEAS-2B cells remarkably, and inhibited mRNA expression levels and protein levels in supernatant of IL-6 and GM-CSF at various concentrations, significantly(p<0.05). However, Hirudo toasted with Talcum(水蛭滑石炒) had no effect on mRNA expression levels and showed a slight inhibitory effect on GM-CSF protein levels in supernatant of culture medium. Conclusions : These results strongly suggest that Hirudo toasted with Ephedrae Herba(水蛭麻黃炒) and Hirudo(水蛭) would be serve as effective medicaments in the treatment of airway inflammation and remodeling of asthmatic patients.

• Korean Journal of Acupuncture
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• v.21 no.2
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• pp.111-123
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• 2004

Objectives : It has been reported that Cordyceps militaris Mycelia(CMM) has an effect on deficiency allergic asthma(虛喘) clinically. The aim of this study was to determine an appropriate oriental treatment and the doses of CMM to treat asthma. Methods : In order to study the effect of herbal acupuncture solution of the CMM on allergic asthma, the mouse were pretreated by CMM herbal acupuncture at BL13, LU4 before antigen sensitization. 2 days later Mice were actively sensitized with a subcutaneous injection of ovalbumin(OA) and 13 days later they were provoked with OA aerosols. IL-4, lymphocyte, macrophage in bronchoalveolar lavage fluid(BALF), IgE in serum, WBC, RBC, HGB in blood, and in vitro isometric contractile responses of the isolated tracheal smooth muscle(TSM) to acetylcholine$(ACh,\;0.1-1000\;{\mu}M)$, KCl were measured. Results : Contractile responses of TSM to ACh were significantly increased in CMM herbal acupuncture 1 group $(Ach\;1000\;{\mu}M)$, CMM herbal acupuncture 2 group $(ACh\;1,\;10\;{\mu}M)$, CMM herbal acupuncture 3 group $(Ach\;0.3,\;1,\;30,\;300\;{\mu}M)$. The sensitivity of TSM to ACh was significantly decreased in CMM herbal acupuncture 3 group. The maximal contractile response of TSM to ACh was significantly decreased in CMM herbal acupuncture 1, 3 group. The maximal contractile response of TSM to KCl was significantly decreased in CMM herbal acupuncture 1, 2, 3 group. The counts of lymphocytes in BALF was significantly increased in CMM herbal acupuncture 3 group. The counts of macrophages in BALF was significantly decreased in CMM herbal acupuncture 3 group. Interleukin-4 level in BALF was significantly increased in CMM herbal acupuncture 1,3 group. and it was increased in CMM herbal acupuncture 2 group, but there was no significance. Serum IgE level was significantly decreased in CMM herbal acupuncture 1, 2, 3 group. The counts of WBC in blood was significantly increased in CMM herbal acupuncture 1, 3 group Conclusion : Based on the above results it is assumed that CMM herbal acupuncture at BL13, LU4 can help the treatment of deficiency allergic Asthm.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.697-704
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• 1998

Background: Asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils in the bronchial mucosa. Asthmatic bronchial mucosa produces many factors described as being chemotactic for inflammatory cells. IL-5, RANTES, and MCP-1 alpha are the chemotactic factors for eosinophils, but their roles are controversial. Recently eotaxin that is a potent eosinophil chemoattractant cytokine was detected in a guinea-pig model of allergic airway inflammation, and human eotaxin was cloned. Eotaxin is a specific chemoattractant for eosinophils, but its role in asthma is not confirmed. We examined the in vivo expression of eotaxin in bronchi of asthmatic patients. Methods : 11 asthmatics and 2 normal controls were enrolled. All subjects were underwent bronchoscopy with bronchial biopsies in 2nd or 3rd carina. RNA extraction from biopsy samples was done by acid-guanidium method. Semi-quantitaive RT-PCR was done for evaluation of eotaxin mRNA expression The extent of eosinophil infiltration was evaluated by counting the eosinophils in submucosa in HPF of microscope. Results : Eotaxin mRNA expressed in symptomatic, uncontrolled asthma. Steroid inhibited expression of eotaxin mRNA in asthma. Expression of eotaxin mRNA correlated with eosinophil infiltration in bronchial tissues. Conclusion: Expression of eotaxin mRNA increases in uncontrolled asthma and eotaxin is involved in the recruitment of eosinophils.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.729-734
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• 1999

Broncho-esophageal fistula(BEF) is an uncommon clinical entity which can cause severe suppurative lung disease. Acquired fistulas between the esophagus and tracheobronchial tree are relatively uncommon. They are caused by many diseases including malignancy and chronic inflammation such as tuberculosis and have favorable outcome with proper treatment To our knowledge, there has been no description of patients with BEF due to the bronchiectasis. We report a case of broncho-esophageal fistula in association with bronchiectasis in a 35-year-old male patient with hemoptysis. Bronchoscopy revealed mild bleeding from the superior segment of the right lower lobe without specific endobronchial lesion. Barium esophagogram could not confirm the fistula. The diagnosis of a broncho-esophageal fistula was established by an esophagogastroscopy using fistulogram and subsequent bronchoscopy, in which the communication between the bronchial tree and the esophagus was demonstrated by instilling dye selectively through the fistulous opening using esophagogastroscopy and visualizing the fistula and the bronchial tree. The patient was treated with resection of the right lower lobe, extirpation of the diverticulum and surgical closure of the bronchial defect and fistula, but he suffered from pneumonia thereafter and eventually expired due to sepsis and multiple organ failure.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.145-153
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• 2007

Background: Asthma is a syndrome that is characterized by a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Colchicine is an inexpensive and safe medication with unique anti-inflammatory properties. IL-1Ra (Interleukin-1 receptor antagonist) mediates the anti-inflammatory effect in human inflammatory diseases, including asthma. This study examined whether IL-1Ra mediates the anti-inflammatory effect of colchicine in normal human bronchial epithelial cells (NHBE), RAW 264.7 cells (murine macrophage cell line), and a mouse lung. Methods: NHBE, RAW 264.7 cells and BALB/c mice were stimulated with colchicine, and the increase in the IL-1Ra level was estimated by ELISA, Western analysis and RT-PCR analysis. Results: Colchicine stimulated NHBE and RAW 264.7 cells to release IL-1Ra into the supernatant in a dose-and time-dependent manner. The major isoform of IL-1Ra in NHBE and RAW 264.7 cells is type I icIL-1Ra, and sIL-1Ra, respectively. IL-1Ra up-regulation was blocked by PD98059, a specific inhibitor in MAPK pathways. Colchicine also stimulated the secretion of IL-1Ra into the bronchoalveolar lavage (BAL) fluid of BALB/c mouse. Conclusion: Colchicine stimulates an increase in the IL-1Ra level both in vivo and in vitro, and might have an anti-inflammatory effect.

• Parasites, Hosts and Diseases
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• v.49 no.4
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• pp.373-380
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• 2011

We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific lgE and lgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-${\alpha}$ (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.