• Journal of Life Science
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• v.16 no.1
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• pp.30-36
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• 2006

Neutrophils are short-lived leukocytes that play a vital role in immune responses to bacteria, yeast, and fungi. This study was performed to investigate the effect of 4-O-methyl-ascochlorin (MAC), an anti-tumor, antibiotic, and anti-fungal prenyl-phenol compound on the spontaneous apoptosis of human neutrophils. MAC time- and dose-dependently accelerated the spontaneous apoptosis of human neutrophils. The effect of MAC on neutrophil apoptosis was blocked by pre-treatment of the neutrophils with specific inhibitors of pancaspase (zVAD-fmk), caspase-8 (zIETD-fmk), or caspase-3 (zDEVD-fmk). The cleavage of procaspase-8 and procaspase-3 was increased by MAC. Mitochondrial permeability, which was measured by the retention of $DiOC_6(3)$, was dose-de-pendently increased by MAC but the change of mitochondrial permeability was not blocked by pretreatment of neutrophils with zIETD-fmk. These results suggest that MAC induces neutrophil apoptosis by caspase-8-dependent but mitochondria-independent manner.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.922-931
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• 2000

Background : It has been well known that bronchia1 asthma is a chronic airway inflammatory disorder. Recently, sputum induced with hypertonic saline was introduced as a simple and useful nonivasive medium to investigate airway inflammation and symptom severity in patients with asthma. We examined the eosinophil, eosinophil cationic protein (ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating facta (GM-CSF), and nitric oxide (NO) derivatives in induced sputum from patients with bronchia1 asthma in order to determine the role of NO and various inflammatory cytokines as a useful markers of airway inflammation or changes in pulmonary function tests and symptoms. Methods : A total 30 patients with bronchia1 asthma received oral prednisolone 30 mg daily for 2 weeks. Forced expiratory volume in one second ($FEV_1$), total blood eosinophil count and induced sputum eosinophil count, ECP, IL-3, IL-5, GM-CSF, and NO derivatives were determined before and after the administration of prednisolone. Results : Of the 30 patients, 13 (43.3%) were male and 17 (56.7%) were female. The mean age of patients was 41.8 years (range 19-64 years). Two patients could not produce sputum at the second study and 3 could not be followed up after their first visit. Two weeks after the prednisolone administration, there was a significant increase in $FEV_1$ (% of predicted value) from 78.1$\pm$20.6 % to 90.3$\pm$ 18.3 % (P<0.001). The eosinophil percentages in induced sputum were significantly decreased after treatment with prednisolone, with values of 56.1$\pm$27.2 % versus 29.6$\pm$21.3 % (P<0.001), and ECP were $134.5\pm68.1\;{\mu}g/L$ versus $41.5\pm42.4\;{\mu}g/L$ (P<0.001) respectively. After the prednisolone treatments, the eotaxin concentration also showed a decreasing tendency from 26.7$\pm$12.8 pg/ml to 21.7$\pm$8.7 pg/ml. There was a decreasing tendency but no significant differences in total blood eosinophil count (425.7$\pm$265.9 vs 287.7$\pm$294.7) and in the concentration of NO derivatives ($70.4\pm44.6{\mu}mol/L$ vs $91.5\pm48.3\;{\mu}mol/L$) after the prednisolone treatments. IL-3, IL-5, GM-CSF were undetectable in the sputum of most subjects either before the prednisolone treatments or after the treatments. Before the prednisolone treatments, a significant inverse correlation was observed between FEV1 and sputum ECP (r=-D.364, P<0.05) and there was a significant correlation between sputum eosinophils and eotaxin (r=0.369, P<0.05) Conclusion : The eotaxin and ECP concentration in induced sputum may be used as markers of airway inflammation after treatments in bronchia1 asthma. In addition, the measurement of sputum eosinophil percent ages is believed to be a simple method displaying the degree of airway inflammation and airway obstruction before and after the prednisolone treatment in bronchia1 asthma. However, unlike exhaled NO, the examination of NO derivatives with Griess reaction in induced sputum is considered an ineffective marker of changing airway inflammation and obstructing symptoms.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.161-171
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• 1999

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-$\alpha$, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-$\alpha$, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-$\alpha$ increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-$\alpha$ may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.