• Journal of Microbiology and Biotechnology
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• 제32권1호
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• pp.81-90
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• 2022

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.

• 대한약침학회지
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• 제7권3호
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• pp.77-88
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• 2004

Objectives ; This study was to investigate the anti-cancer effects of herbal acupuncture with distilled fresh ginseng. The herbal acupuncture was injected to Chung-wan($C.V_{12}$) and Wisu($BL_{21}$) of mice that were subjected to Sarcoma-180 adbominal cancer cell and A549 human epithelial lung cancer cells in vitro. Methods : Anti-cancer effects of distilled fresh ginseng herbal acupuncture were tested by measruing Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro. And four weeks old Balb/c line male mice weighing around $20\;{\pm}\;3g$ were used to measure survival rate and anti-cancer effect to outputs of interleukin-2 and interleukin-4 using flow cytometry, possibility of mRNA menifestation using RT-PCR, and Cox mRNA. The results are as follows. Results : 1. In measuring mRNA menifestation in Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro, the result showed that fresh ginseng decreased Cox-2 which is directly involved in Inflammation process. 2. Survival rate was measured in an anti-cancer effect experiment against Sarcoma-180 abdorminal cancer. Median survival time of controlled group was 27 days, of experiment group I was 21 days, and of experiment group II was 27 days. Therefore, experiment group I showed -22.2% increase in survival rate and experiment group II showed no difference compare to controlled group. 3. There was no difference between condition group and controlled and experiment group in measuring outputs of interleukin-2 and interleukin 4 by using flow cytometry 4. In measuring outputs of interleukin-2 by using ELISA, there was no significant difference between condition group and controlled group and there was decrease in experiment group II compared to conditioned and controlled group. 5. In measuring cytokine mRNA menifestation by using RT-PCR, experiment group I showed increase of mRNA menifestation in interleukin-2,4 and $interferon-{\gamma}$ and experiment group II showed no significant difference in $interferon-{\gamma}$. Conclusion : According to the results, fresh ginseng herbal-acupuncture took a little effects in cancer. In using distilled fresh ginseng herbal acupuncture has effect on Cox-2 decrease. However, the difference in concentration of fresh ginseng showed no effect on killing cancer cell. It is assumed that inaccurate concentration of herbal acupuncture and fresh ginseng component could be the reason for this result. Therefore, future consideration will be studies on herbal acupuncture concentration.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.238-245
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• 2007

Chronic formaldehyde inhalation studies have suggested its relativity to teratogenicity, cancer incidence, neurodegenerative and vascular disorders. Many toxicological data on the formaldehyde toxicity are available, but proteomic results showing complete protein profiles are limited. Therefore, alterations of protein expression patterns upon formaldehyde treatment were investigated in the human lung epithelial cell line. Differentially expressed proteins following formaldehyde treatment were analyzed on 2-dimensional gels, and further analyzed by MALDI-TOF to identify the proteins. Among the identified proteins, 24 proteins were notably up-regulated and 6 proteins were down-regulated. In particular, cytoskeleton related protein named vinculin and Rho GDP dissociation inhibitor which plays a key role in apoptosis increased remarkably.

• 환경위생공학
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• 제7권2호
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• pp.95-110
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• 1992

Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10495-10500
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• 2015

Background: To evaluate the effects of bufalin in A549 human lung adenocarcinoma epithelial cells in vitro and assess the underlying mechanisms. Materials and Methods: Human A549 non-small cell lung cancer (NSCLC) cells were treated with various concentrations of bufalin. Cell proliferation was measured by CCK-8 assay, apoptotic cell percentage was calculated by flow cytometry and morphological change was observed by inverted phase contrast microscopy/transmission electron microscopy. In addition, the membrane potential of mitochondria was detected by JC-1 fluorescence microscopy assay, and the related protein expression of cytochrome C and caspase-3 was analyzed by Western blotting. Results: Bufalin could inhibit the proliferation of A549 cells via induction of apoptosis, with the evidence of characteristic morphological changes in the nucleus and mitochondria. Furthermore, bufalin decreased the mitochondrial membrane potential with up-regulation of cytochrome C in the cytosol, and activation of caspase-3. Conclusions: Bufalin inhibits the proliferation of A549 cells and triggers mitochondria-dependent apoptosis, pointing to therapeutic application for NSCLC.

• Journal of Ginseng Research
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• 제48권1호
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• pp.77-88
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• 2024

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

• Environmental Analysis Health and Toxicology
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• 제19권1호
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• pp.59-64
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• 2004

Metallothionein gene expression of diesel exhaust particles (DEP) was investigated in human lung epithelial cell line. DEP was collected from diesel motor bus and soluble fraction in water was obtained. Cells, grown to near confluence, were exposed to 5-50 ppm DEP for 6 hours. Regarding the metallothionein gene expressions, MT-1 and MT-2 were induced in the DEP-treated cell by using RT-PCR and real-time PCR. However, MT-3 which is known to be brain specific, and another isoform MT-4 were not expressed in cadmium-treated groups as well as control group. Heavy metal of DEP was also analyzed and Zn was found as the major component of heavy metals in DEP used in this study.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6321-6326
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• 2013

Introduction: Lung cancer is extremely harmful to human health and has one of the highest worldwide incidences of all malignant tumors. Approximately 80% of lung cancers are classified as non-small cell lung cancers (NSCLCs). Cisplatin-based multidrug chemotherapy regimen is standard for such lesions, but drug resistance is an increasing problem. F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein family that regulates cell cycle progression, and cell growth and differentiation. FBW7 also functions as a tumor suppressor. Methods: We used cell viability assays, Western blotting, and immunofluorescence combined with siRNA interference or plasmid transfection to investigate the underlying mechanism of cisplatin resistance in NSCLC cells. Results: We found that FBW7 upregulation significantly increased cisplatin chemosensitivity and that cells expressing low levels of FBW7, such as NCI-H1299 cells, have a mesenchymal phenotype. Furthermore, siRNA-mediated silencing or plasmid-mediated upregulation of FBW7 resulted in altered epithelial-mesenchymal transition (EMT) patterns in NSCLC cells. These data support a role for FBW7 in regulating the EMT in NSCLC cells. Conclusion: FBW7 is a potential drug target for combating drug resistance and regulating the EMT in NSCLC cells.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.71-78
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• 1997

In an attempt to investigate the role of phospholipase $A_2$($PLA_2$) in interleukin-l (IL-l) induced acute lung injury, mepacrine was tried to inhibit $PLA_2$ in IL-l induced ARDS rats. For confirmation of acute lung injury by IL-l, and to know the role of neutrophils in this injury, lung leak index, lung myeloperoxidase(MPO), number of neutrophils and protein content in the bronchoalveolar lavage (BAL) and wet lung weight were measured. At the same time lung $PLA_2$ was measured to know the effect of IL-l on $PLA_2$ activity. Pulmonary surfactant was also measured for an investigation of type II alveolar cell function. Neutrophil adhesion assay was performed to know the effect of $PLA_2$ inhibition in vitro with human umbilical vein endothelial cells (HUVEC). For precise location of injury by IL-l, morpholgical study was performed by electron microscopy. Five hours after instillation of IL-l (50 ng/rat), lung leak index, protein content, number of neutrophils, lung MPO and wet lung weight were increased significantly. Five hours after IL-l instillation lung $PLA_2$ activity was increased significantly, and increased surfactant release was observed in IL-l induced ARDS rats' BAL. In contrast, in rats given mepacrine and IL-l, there was decrease of acute lung injury i.e. decrease of lung leak index, wet lung weight, protein content, number of neutrophils in BAL and decreased lung MPO activity. Mepacrine decreased surfactant release also. Interestingly, inhibition of $PLA_2$ decreased adhesion of human neutrophils to HUVEC in vitro. Morphologically, IL-l caused diffuse necrosis of endothelial cells, type I and II epithelial cells and increased the infiltration of neutrophils in the interstitium of the lung but after mepacrine treatment these pathological findings were lessened. On the basis of these experimental results it is suggested that $PLA_2$ has a major role in the pathogenesis of acute lung injury mediated by neutrophil dependent manner in IL-l induced acute lung injury.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.161-168
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• 2017

Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-$1{\alpha}$ and K562) in vitro using $Transwell^{(R)}$ co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-$1{\alpha}$ and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.