• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.223-235
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• 2000

Background: Liquid ventilation is associated with decreased inflammatory response in an injured lung. This study was performed to investigate if whether perfluorocarbon(PFC) can decrease chemokine expression in airway epithelial cells. Methods: A549 cells were used for airway epithelial cells and perfluorodecalin for PFC. To expose cells to PFC, lower chamber of Transwell$^{(R)}$plate was used. This study was performed in two parts. In the first part, we examined whether PFC could decrease chemokine expression in airway epithelial cells through inhibition of other inflammatory cells. Peripheral blood mononuclear cells(PBMC's) were isolated and stimulated with lipopolysaccharide(LPS, 10 ${\mu}g/mL$) for 24 hours with or without exposure to PFC. Then A549 cells were stimulated with conditioned media(CM) containing the culture supernatants of PBMC. After 24 hours, the expressions of interleukin-8(IL-8) and RANTES were measured. In the second part of the study, we studied whether PFC could directly suppress chemokine expression in airway epithelial cells. A549 cells were stimulated for 24 hours with interleukin-l$\beta$ and/or tumor necrosis factor-$\alpha$ with or without exposure to PFC, and then the chemokine expression was measured. Northern analysis was used to measure the mRNA expression, and ELISA was used for immunoreactive protein measurements in culture supernatant. Results: 1. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by CM from LPS-stimulated PBMC in A459 cells compared to with CM from unstimulated PBCM (p<0.05), but exposure of PFC had no significant effect on either mRNA expression or immunoreactive protein expression. 2. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by IL-1$\beta$ and TNF-$\alpha$ in A549 cells(p<0.05), but exposure of PFC had no significant effect on neither either mRNA expression nor immunoreactive protein production. Conclusion : Decreased chemokine expression of airway epithelial cells may not be involved in decreased inflammatory response observed in liquid ventilation. Further studies on possible mechanisms of decreased inflammatory response are warranted.

• Tuberculosis and Respiratory Diseases
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• v.81 no.2
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• pp.132-137
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• 2018

Background: The pathophysiology of chronic obstructive pulmonary disease (COPD) includes inflammation, oxidative stress, an imbalance of proteases and antiproteases and apoptosis which has been focused on lately. Abnormal apoptotic events have been demonstrated in both epithelial and endothelial cells, as well as in inflammatory cells including neutrophils and lymphocytes in the lungs of COPD patients. An increased propensity of activated T lymphocytes to undergo apoptosis has been observed in the peripheral blood of COPD patients. Therefore, the apoptosis of T lymphocytes without activating them was investigated in this study. Methods: Twelve control subjects, 21 stable COPD patients and 15 exacerbated COPD patients were recruited in the study. The T lymphocytes were isolated from the peripheral blood using magnetically activated cell sorting. Apoptosis of the T lymphocytes was assessed with flow cytometry using Annexin V and 7-aminoactinomycin D. Apoptosis of T lymphocytes at 24 hours after the cell culture was measured so that the T lymphocyte apoptosis among the control and the COPD patients could be compared. Results: Stable COPD patients had increased rates of $CD4^+$ T lymphocyte apoptosis at 24 hours after the cell culture, more than the $CD4^+$ T lymphocyte apoptosis which appeared in the control group, while the COPD patients with acute exacerbation had an amplified response of $CD4^+$ T lymphocyte apoptosis as well as of $CD8^+$ T lymphocyte apoptosis at 24 hours after the cell culture. Conclusion: Stable COPD patients have more apoptosis of $CD4^+$ T lymphocytes, which can be associated with the pathophysiology of COPD in stable conditions.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• BMB Reports
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• v.53 no.7
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• pp.367-372
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• 2020

Cell cycle-related kinase (CCRK) has a conserved role in ciliogenesis, and Ccrk defects in mice lead to developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, retinal degeneration, and polycystic kidney. Here, we found that Ccrk is highly expressed in mouse trachea and bronchioles. Ccrk mutants exhibited pulmonary hypoplasia and abnormal branching morphogenesis in respiratory organ development. Furthermore, we demonstrated that Ccrk mutant lungs exhibit not only impaired branching morphogenesis but also a significant sacculation deficiency in alveoli associated with reduced epithelial progenitor cell proliferation. In pseudoglandular stages, Ccrk mutant lungs showed a downregulation of Hedgehog (Hh) signaling and defects in cilia morphology and frequency during progenitor-cell proliferation. Interestingly, we observed that activation of the Hh signaling pathway by small-molecule smoothened agonist (SAG) partially rescued bud morphology during branch bifurcation in explants from Ccrk mutant lungs. Therefore, CCRK properly regulates respiratory airway architecture in part through Hh-signal transduction and ciliogenesis.

• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.663-672
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• 2006

Background: $PM_{10}$(Particulate matter with a diameter ($<10{\mu}m$), which is characterized by different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also produce unique particulate matter in affected areas. This study investigated the cytokine produced by A549 epithelial cells exposed to particles collected during both the Asian dust pfenomenon and ambient air particles in a non-dusty period. Method: Air samples were collected using a high volume air sampler(Sibata Model HV500F) with an air flow at $500{\ell}/min$ for at least 6 hours. The cytokine messenger RNA(mRNA) was measured using a reverse transcriptase polymerase chain reaction(RT-PCR). The A549 cells were exposed to 10 to $500{\mu}g/m{\ell}$ of a suspension containing $PM_{10}$ for 24 hours. Each was compared with those in the non-exposed control cells. Result: The mRNA levels of interleukin(IL)-$1{\alpha}$, $IL-I{\beta}$, IL-8, and the granulocyte macrophage colony stimulating factor(GM-CSF) increased after veing exposed to $PM_{10}$ in the ambient air particles, compared with those in the non-exposed control cells. The increase in $IL-1{\alpha}$ and IL-8 were dose dependent at a $PM_{10}$ concentration between $100{\mu}g/m{\ell}$ and $500{\mu}g/m{\ell}$. The mRNA level of IL-8 in the A549 epithelial cells was higher during the in the Asian dust period($500{\mu}g/m{\ell}$) than during the non dust period. Conclusion: A549 cells exposed to the $PM_{10}$ collected during the Asian dust period produce more proinflammatory cytokine than during non-dusty period. This cytokine enhances the local inflammatory response in the airways and can also contribute to the systemic component of this inflammatory process.

• The Korean Journal of Cytopathology
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• v.8 no.1
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• pp.76-82
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• 1997

Two cases of pulmonary atypical carcinoid tumor were diagnosed by fine needle aspiration cytology. Although the cytologic features of atypical carcinoid tumor have been relatively well described, it is easy to confuse atypical carcinoid tumor with typical carcinoid tumor, small cell carcinoma and adenocarcinoma of the lung. Atypical carcinoid tumor has been recognized as a distinct variant of pulmonary neuroendocrine carcinoma, with characteristic histopathologic and clinical features that separate it from both carcinoid and small cell carelnoma. The distinction of atypical carcinoid tumor from small cell carcinoma has important prognostic and therapeutic implications. The cytologic characteristics of atypical carcinoid tumor included polygonal to fusiform cells with a variable amount of lacy cytoplasm, oval nuclei with coarsely dispersed chromatin and frequent nucleoli, and mild pleomorphism. The malignant cells were arranged either in acinus-like clusterg or in epithelial sheets.

• Natural Product Sciences
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• v.25 no.2
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• pp.103-110
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• 2019

We investigated the anti-inflammatory effect of Pyunkang-tang extract (PGT), a complex herbal extract based on traditional Chinese medicine that is used in Korea for controlling diverse pulmonary diseases, on cigarette smoke-induced pulmonary pathology in a rat model of chronic obstructive pulmonary disease (COPD). The constituents of PGT were Lonicerae japonica, Liriope platyphylla, Adenophora triphilla, Xantium strumarinum, Selaginella tamariscina and Rehmannia glutinosa. Rats were exposed by inhalation to a mixture of cigarette smoke extract (CSE) and sulfur dioxide for three weeks to induce COPD-like pulmonary inflammation. PGT was administered orally to rats and pathological changes to the pulmonary system were examined in each group of animals through measurement of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) levels in bronchoalveolar lavage fluid (BALF) at 21 days post-CSE treatment. The effect of PGT on the hypersecretion of pulmonary mucin in rats was assessed by quantification of the amount of mucus secreted and by examining histopathologic changes in tracheal epithelium. Confluent NCI-H292 cells were pretreated with PGT for 30 min and then stimulated with CSE plus PMA (phorbol 12-myristate 13-acetate), for 24 h. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. The results were as follows: (1) PGT inhibited CSE-induced pulmonary inflammation as shown by decreased TNF-${\alpha}$ and IL-6 levels in BALF; (2) PGT inhibited the hypersecretion of pulmonary mucin and normalized the increased amount of mucosubstances in goblet cells of the CSE-induced COPD rat model; (3) PGT inhibited CSE-induced MUC5AC mucin production and gene expression in vitro in NCI-H292 cells, a human airway epithelial cell line. These results suggest that PGT might regulate the inflammatory aspects of COPD in a rat model.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.449-458
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• 2003

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

• Tuberculosis and Respiratory Diseases
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• v.67 no.2
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• pp.131-134
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• 2009

Pulmonary papillomas are rare benign epithelial neoplasms arising in bronchial surface epithelium. They are categorized by a variety of cell types including squamous, glandular, and mixed squamous and glandular type. Among them, glandular papilloma is extremely rare and has not been reported in Korea. The patient was a 52 year-old man presenting with a 4-months' history of recurrent hemoptysis. Bronchofiberoscopy revealed a whitish, glistening, and polypoid mass lesion at the proximal bronchus in the basal segment of the left lower lung. Bronchoscopic biopsy was performed; papillary fronds lined by ciliated or nonciliated pseudostratified columnar epithelium were noted on histologic findings. We present the first case of glandular papilloma in Korea. Two years later, the patient visited our hospital again due to hemoptysis. On follow-up bronchoscopy, a mass that had been found previously showed an increase in size.