• IMMUNE NETWORK
• /
• v.16 no.3
• /
• pp.165-175
• /
• 2016

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

• Tuberculosis and Respiratory Diseases
• /
• v.53 no.2
• /
• pp.127-135
• /
• 2002

Background : Idiopathic interstitial pneumonia is characterized by chronic inflammation and pulmonary fibrosis. The clara cell 10 kD protein (CC10, also designated CC16) is synthesized by the bronchial epithelium and has been suggested to have a potent anti-inflammatory effect. Therefore, CC-10 might be a candidate for controlling the inflammatory events in patients with idiopathic interstitial pneumonia. The aim of this study was to determine if the degrees of pulmonary fibrosis in idiopathic interstitial pneumonia is associated with CC-10 in the BAL fluid. Materials and Methods : The BAL fluid was collected from 29 patients and 10 controls. Densitometric analysis of the western blot assay for the CC-10 was subsequently performed. The RI (relative intensity) of each band was compared according to the diagnosis, the radiological degrees of pulmonary fibrosis and the relative proportion of inflammatory cells in the BAL fluid. Results : There were no differences in the CC-10 expression levels in the BAL fluid between the patients (RI $77.5{\pm}75.8%$) and the controls ($70.7{\pm}39.8%$) (p>0.05). In addition, the degrees of pulmonary fibrosis and airway inflammation in patients with usual interstitial pneumonia were not associated with CC-10 expression in the BAL fluid (p>0.05). Conclusion : This study suggests that CC-10 expression is not associated with the degrees of pulmonary fibrosis in patients with usual interstitial pneumonia.

• Biomedical Science Letters
• /
• v.9 no.1
• /
• pp.37-42
• /
• 2003

The present study was conducted to determine whether administration of heat extract of Lepidii Semen has an inhibitory effect on neutrophil-derived oxidative injury following dermal scald burn in rats. Acute lung injury was induced by scald burn (15% of TBSA) in rats. To identify acute edematous lung injury, protein concentrations and numbers of polymorphonuclear leukocytes were measured in bronchoalveolar lavage (BAL) at 5 h after skin burn. In addition, the level of lung KC (neutrophil chemoattractant cytokine) and activity of lung myeloperoxidase (MPO) were measured, and histopathological changes were observed as well. Lung weight and concentration of BAL protein, the index of lung injury, were clearly increased at 5 h postburn compared with those of sham-operated group. Administration of heat extract of Lepidii Semen after scald burn inhibited the production of KC in lung tissue and decreased the activity of lung MPO related to infiltration of neutrophils. In histopathological changes in lung tissue, infiltration of inflammatory cells and pulmonary edema induced by skin burn were decreased by administration of heat extract of Lepidii Semen after scald burn. These results suggest that Lepidii Semen may be an effective medical stuff for acute lung injury induced by skin burn.

• Genomics & Informatics
• /
• v.4 no.2
• /
• pp.65-70
• /
• 2006

Peptide mass mapping is the matching of experimentally generated peptides masses with the predicted masses of digested proteins contained in a database. To identify proteins by matching their constituent fragment masses to the theoretical peptide masses generated from a protein database, the peptide mass fingerprinting technique is used for the protein identification. Thus, it is important to know the theoretical mass distribution of the database. However, few researches have reported the peptide mass distribution of a database. We analyzed the peptide mass distribution of non-redundant protein sequence database in the NCBI after digestion with 15 different types of enzymes. In order to characterize the peptide mass distribution with different digestion enzymes, a power law distribution (Zipfs law) was applied to the distribution. After constructing simulated digestion of a protein database, rank-frequency plot of peptide fragments was applied to generalize a Zipfs law curve for all enzymes. As a result, our data appear to fit Zipfs law with statistically significant parameter values.

• The Korean Journal of Physiology and Pharmacology
• /
• v.9 no.2
• /
• pp.69-75
• /
• 2005

TRPM7, a cation channel protein permeable to various metal ions such as $Mg^{2+}$, is ubiquitously expressed in variety of cells including lymphocytes. The activity of TRPM7 is tightly regulated by intracellular $Mg^{2+}$, thus named $Mg^{2+}$-inhibited cation (MIC) current, and its expression is known to be critical for the viability and proliferation of B lymphocytes. In this study, the level of MIC current was compared between immature (WEHI-231) and mature (Bal-17) B lymphocytes. In both cell types, an intracellular dialysis with $Mg^{2+}$-free solution (140 mM CsCl) induced an outwardly-rectifying MIC current. The peak amplitude of MIC current and the permeability to divalent cation ($Mn^{2+}$) were several fold higher in Bal-17 than WEHI-231. Also, the level of mRNAs for TRPM7, a molecular correspondence of the MIC channel, was significantly higher in Bal-17 cells. The amplitude of MIC was further increased, and the relation between current and voltage became linear under divalent cation-free conditions, demonstrating typical properties of the TRPM7. The stimulation of B cell receptors (BCR) by ligation with antibodies did not change the amplitude of MIC current. Also, increase of extracellular $[Mg^{2+}]_c$ to enhance the $Mg^{2+}$ influx did not affect the BCR ligation-induced death of WEHI-231 cells. Although the level of TRPM7 was not directly related with the cell death of immature B cells, the remarkable difference of TRPM7 might indicate a fundamental change in the permeability to divalent cations during the development of B cells.

• Journal of Life Science
• /
• v.21 no.8
• /
• pp.1100-1108
• /
• 2011

The immunomodulating effects of moxifloxacin seem to be effective in downregulating inflammatory reactions. This presumed effect was tested in endotoxin (ETX)-induced acute lung injury (ALI) in rats. After moxifloxacin treatment (10 mg/kg) of ETX-given rats, lung myeloperoxidase (MPO) activity, bronchoalveolar-lavage (BAL) protein, and the number of neutrophils in the BAL cells were measured. Light and electron microscopic structures were also examined. Electron microscopic $CeCl_3$ histochemistry for the detection of hydrogen peroxide in the lungs and immunohistochemistry of cytosolic phospholipase A2 (cPLA2) in the lung tissues and BAL cells were performed. To examine the expression of TNF${\alpha}$ in the lungs, western blotting was carried out with the lung tissues. ETX had accumulated neutrophils in the lungs, which was followed by lung leak. Oxidative stress occurred, and increased expression of cPLA2 in the lung tissues and BAL cells was observed in the ETX-given rats. Simultaneously, the expression of TNF${\alpha}$ was enhanced by ETX. Moxifloxacin, however, decreased all these parameters, indicating that ALI may have been ameliorated. Moxifloxacin appears to ameliorate ETX-induced ALI partially through the suppression of cPLA2 in the lungs of rats.

• Tuberculosis and Respiratory Diseases
• /
• v.85 no.1
• /
• pp.18-24
• /
• 2022

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (T_H2)/T_H17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

• Tuberculosis and Respiratory Diseases
• /
• v.39 no.4
• /
• pp.334-342
• /
• 1992

Background: The activated T lymphocyte by inhalaed mycobacterial antigen may evoke cell-mediated immunity in patients with active pulmonary tuberculosis. These activated lymphocyte may influence the response of tuberculin-purified protein derivative (PPD) in skin test. But occasionally, anergy to PPD appear in patients with pulmonary tuberculosis in spite of active stage. Thus we evaluated the effect of change of subtypes of lymphocyte in bronchoalveolar lavage fluid (BAL) and peripheral blood on anergy to PPD in patients with active pulmonary tuberculosis. Method: We performed tuberculin skin test and flow-cytometry analysis of lymphocytes obtained from BAL fluid and peripheral blood in 11 healthy normal volunteers and 20 patients with active pulmonary tuberculosis. Results: 1) The composition of lymphocyte significantly increased in patients with active pulmonary tuberculosis when compared with that in healthy control ($25.2{\pm}4.8$ vs $6.5{\pm}1.3%$, p<0.01), but composition of monocyte significantly decreased ($69.6{\pm}5.7$ vs $89.2{\pm}1.4%$, p<0.05) in analysis of BAL fluid. 2) There were no differences in compositions of cells in BAL fluid between responders and no-responders to PPD. 3) The compositions of CD3 (+), CD4 (+), CD3 (+) IL-2R (+), CD3 (+) HLA-DR (+) significantly increased in BAL fluid when compared with those in peripheral blood in patients with active pulmonary tuberculosis. But the composition of CDS (+), CD4/CDS were not different between BAL fluid and peripheral blood. 4) There were no correlations between response to PPD and compositions of cells and lymphocyte subtypes in BAL fluid and peripheral blood in all patients with tuberculosis, responders, and no-responders, respectively. Conclusion: From these results, we suggest no direct relationship between compositions of inflammatory cells in bronchoalveolar lavage fluid and we could not rule out the possibility of compartmentalization of activated lymphocyte involving in anergy to PPD in skin test in patients with active pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.3
• /
• pp.219-229
• /
• 2002

Background : Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an important mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin ALI has not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. Materials and Methods : The study consisted of 4 groups using Sprague-Dawley rats : 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the $H_2$ receptor antagonist-treated group ($H_2$ group) and 4) the $H_1$ receptor antagonist-treated group ($H_1$ group), where $H_2$-receptor blocker (ranitidine) and $H_1$-receptor blocker(pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using $I^{125}$-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase(MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-$\alpha$, IL-$1{\beta}$ and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. Results : Compared to the control group, the endotoxin group exhibited significant increases in all lung injury indices. Significant reductions in the endotoxin-mediated increases in lung leak index (p<0.05) were observed in both the $H_1$ and $H_2$ groups. In addition the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the $H_2$ group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the $H_2$ and $H_1$ groups compared to the endotoxin group. The increases in TNF-$\alpha$ IL-$1{\beta}$ and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the $H_2$ and $H_1$ groups. Conclusion : Antihistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the $H_2$ receptor. However the attenuating mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.

• Journal of Chest Surgery
• /
• v.35 no.5
• /
• pp.343-349
• /
• 2002

background: In an attempt to investigate the role of oxidants in the activation of phospholipase $A_2$(PLA$_2$) and endogenous oxidative stress in the lung. acute inflammatory lung injury was induced by the instillation of hydrogen peroxide into the trachea of Sprague-Dawley rats. Material and Method: To prove the hypothesis thats released oxidants from neutrophils activate the PLA$_2$ retrogradely, activities of PLA$_2$ and lysoplatelet activating factor acetyltransferase(lysoPAF AT) were assayed i hours after instillation of hydrogen peroxide. In addition, to confirm the impairing effects of the activation of PLA$_2$ associated with endogenous oxidative stress, lung weight/body weight ratio(L$\times$10$^{-3}$ B), protein contents(mg/two lungs) in bronchoalveolar lavage(BAL) were measured. As neutrophilic respiratory burst has been known to play a pivotal role in the genesis of endogenous oxidative stress associated with acute inflammatory lung injury, BAL neutrophils counts and level of lung myelperoxidase(MPO) were measured after hydorgen peroxide insult. Morphological and histochemical studies were also performed to identify the effect of the endogenous oxidative stress. Result: Five hours after hydrogen peroxide instillation, lungs showed marked infiltration of neutrophils and increased weight. Protein contents in BAL increased significantly compared to those of normal rats. PLA$_2$ activity was enhanced in the hydrogen peroxide instilled group. Interestingly, the accelerated production of platelet activating factor(PAF) was confirmed by the increased activity of lysoPAF AT in the $H_2O$$_2$ employed lung. Morphologically, light microscopic findings of lungs after instillation of hydrogen peroxide showed atelectasis and infiltration of inflammatory cells, which was thought to be caused by lipid mediators produced by PLA$_2$ activation. In cerium chloride cytochemical electron microscopy, dense deposits of cerrous perhydroxide were identified. In contrast, no deposit of cerrous perhydroxide was found in the normal lung.