• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4995-5000
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• 2014

Background: Cancer constitutes a key pressure on public health regardless of the economy state in different countries. As a kind of highly malignant epithelial tumor, lacrimal gland adenoid cystic carcinoma can occur in any part of the body, such as salivary gland, submandibular gland, trachea, lung, breast, skin and lacrimal gland. Chemotherapy is one of the key treatment techniques, but drug resistance, especially MDR, seriously blunts its effects. As an element of the 60S large ribosomal subunit, the ribosomal protein L39-L gene appears to be documented specifically in the human testis and many human cancer samples of different origins. Materials and Methods: Total RNA of cultured drug-resistant and susceptible lacrimal gland adenoid cystic carcinoma cells was seperated, and real time quantitative RT-PCR were used to reveal transcription differences between amycin resistant and susceptible strains of lacrimal gland adenoid cystic carcinoma cells. Viability assays were used to present the amycin resistance difference in a RPL39-L transfected lacrimal gland adenoid cystic carcinoma cell line as compared to control vector and null-transfected lacrimal gland adenoid cystic carcinoma cell lines. Results: The ribosomal protein L39-L transcription level was 6.5-fold higher in the drug-resistant human lacrimal gland adenoid cystic carcinoma cell line than in the susceptible cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells revealed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions: The ribosomal protein L39-L gene could possibly have influence on the drug resistance mechanism of lacrimal gland adenoid cystic carcinoma cells.

• 한국식품과학회지
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• 제53권2호
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• pp.165-173
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• 2021

본 연구에서는 UPM에 의해 유발되는 NCI-H441 세포 내 ROS 생성과 그에 따른 tight junction 단백질(N-cadherin, fibronectin, occluding, ZO-1, 및 claudin-4 등)의 발현 억제를 확인하였고 ECL의 전처리로 인하여 해당 ROS 생성 및 tight junction 단백질 발현 억제 현상이 완화되는 보호효과를 확인하였다. 그 결과, 폐 세포에서 UPM에 의해 유발된 산화 스트레스 및 tight junction 단백질의 발현 감소가 ECL을 선 처리함으로써 억제되어 결과적으로 산화 스트레스와 같은 미세먼지에 의한 폐 손상으로부터 보호 효과를 나타내고 tight junction 수준의 유지를 확인하였다. 이러한 결과를 통해 ECL 추출물은 폐와 기관지의 보호효과를 나타내며 폐 관련 질병의 예방효과가 있는 기능성 천연 물질로써 활용이 가능할 것으로 기대된다.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.268-272
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• 2021

Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.

• 한국자원식물학회지
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• 제22권6호
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• pp.552-557
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• 2009

Allicin, a garlic componente, is believed to provide protection against various diseases including inflammation. Since interactions of the cell adhesion molecules are known to play important roles in mediating inflammation, inhibiting adhesion protein upregulation is a possible therapeutic target. In this study, we demonstrate that TNF-${\alpha}$- and catalase-induced expression of ICAM-1 on human lung epithelial cells (A549) in a dose-dependent manner and catalase expression and activity were also increased in TNF-${\alpha}$-treated cells. Treatment of the TNF-${\alpha}$-treated cells with catalase inhibitor 3-amino-1,2,4-triazole resulted in a significant decreased the level of ICAM-1. These data suggest that induction of ICAM-1 expression by TNF-${\alpha}$ is associated with catalase. In addition, allicin was found to inhibit the TNF-${\alpha}$ induced expression of ICAM-1 on the A549 cells. This compound also inhibited the production of catalase induced by TNF-${\alpha}$, which suggests that the inhibition of ICAM-1 expression by allicin may be due to the modulated production of catalase.

• Nutrition Research and Practice
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• 제11권6호
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• pp.461-469
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• 2017

BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. MATERIALS/METHOD: This study employed $2{\mu}g$/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 ${\mu}g$/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ${\geq}50$ mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.

• Tuberculosis and Respiratory Diseases
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• 제63권2호
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• pp.145-153
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• 2007

연구배경: 천식은 기류장애, 기도과민성 및 기도염증을 특징으로 하는 질환이다. 콜히친은 안전하고 저렴한 항염증 면역조절제로서 천식치료에 효과가 있다는 보고가 있으며, IL-1Ra는 천식을 포함한 인체 내 염증질환에 있어 항염증효과를 매개하는 대표적인 물질이다. 본 연구에서는 기도 내에서 콜히친에 의한 항염증작용이 IL-1Ra에 의해 매개될 수 있다는 가설을 세우고 이를 실험적으로 증명하고자 하였다. 방법: 정상 인체 기관지 상피세포와 RAW 264.7 세포, BALB/c 쥐에게 콜히친을 투여한 후 IL-1Ra의 생성을 ELISA, Western분석, RT-PCR 을 통해 측정하였다. 결과: 정상 인체 기관지 상피세포에서 콜히친의 투여농도가 증가함에 따라, 또한 투여 후 시간이 지남에 따라 IL-1Ra의 생성이 증가하였다. 이러한 IL-1Ra의 증가는 대표적인 MAPK경로 억제제인 PD98059에 의해 억제되었다. 콜히친의 IL-1Ra 자극효과는 BALB/c 쥐의 기관지 폐포세척액과 폐조직에서도 관찰되었다. 결론: 기도에서 콜히친은 생체 내와 생체 외에서 IL-1Ra의 생성을 유도하고 IL-1Ra를 통한 항염증 작용을 할 것으로 보이며, 적어도 콜히친에 의한 IL-1Ra의 생성에는 MAPK경로가 관여할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제79권4호
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.

• Parasites, Hosts and Diseases
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• 제61권1호
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• pp.60-71
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• 2023

Cockroaches can cause allergic sensitization in humans via contact with their feces or frass. Antibiotics can affect concentration of major allergen and total bacteria production in German cockroaches (Blattella germanica). This study examined the ability of antibiotic-treated German cockroaches to induce allergic airway inflammation and the effect of antibiotics on their lipopolysaccharide and Bla g1, 2, and 5 expression levels. Specifically, we measured the ability of German cockroach extract (with or without prior antibiotic exposure) to induce allergic inflammation in human bronchial epithelial cells and a mouse model of asthma. Bacterial 16S rRNA and lipopolysaccharide levels were lower in ampicillin-treated cockroaches than in the control group. The Bla g1, Bla g2, and Bla g5 expression in ampicillin-treated cockroaches decreased at both the protein and RNA levels. In human bronchial epithelial cell lines BEAS-2B exposed to the ampicillin-treated extract, expression levels of interleukin-6 and interleukin-8 were lower than that in the control group. The total cell count and eosinophil count in bronchoalveolar lavage fluid was also lower in mice exposed to the ampicillin-treated extract than in those exposed to normal cockroach extract. Mouse lung histopathology showed reduced immune cell infiltration and mucus production in the ampicillin group. Our results showed that ampicillin treatment reduced the symbiont bacterial population and major allergen levels in German cockroaches, leading to reduced airway inflammation in mice. These results can facilitate the preparation of protein extracts for immunotherapy or diagnostics applications.

• 대한의생명과학회지
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• 제28권3호
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• pp.192-194
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• 2022

The trophic factor Neuregulin-1 (NRG-1) plays a critical role in the development of the peripheral nervous system and the repair of nerve injuries. The regulation of neutrophil apoptosis by cytokine secretion from structural cells is an important process in inflammatory diseases, including asthma. This study aimed to investigate the relationship between NRG-1 and the alteration of neutrophil apoptosis by the regulation of cytokine release in the human lung epithelial BEAS-2B cells. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) induce the increase in the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). NRG-1 alone had no effect on the secretion of IL-6, IL-8, and MCP-1. However, co-treatment of TNF-α and IFN-γ with NRG-1 inhibited the secretion of IL-6, IL-8, and MCP-1 that had been increased by TNF-α and IFN-γ. Treatment with NRG-1 did not have a direct effect on neutrophil apoptosis. Co-treatment of TNF-α and IFN-γ with NRG-1 was not effective on suppression of neutrophil apoptosis due to TNF-α and IFN-γ. The supernatant of BEAS-2B cells after co-treatment of TNF-α and IFN-γ with NRG-1 suppressed the inhibition of neutrophil apoptosis that had been caused due to the supernatant treated with TNF-α and IFN-γ. Taken together, NRG-1 has an anti-inflammatory effect in an inflammatory milieu by the regulation of cytokine secretion and neutrophil apoptosis.

• 대한한의학회지
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• 제29권4호
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• pp.146-160
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• 2008

Objectives: The present study was designated to evaluate the direct effects of Fructus Liquidambaris on suppression of eosinophil activity and on suppression of chemokines such as eotaxin, IL-8, ICAM-1, and VCAM-1, in vitro. Methods: A549 cells were stimulated with TNF-$\alpha$ (100 ng/ml), IL-4 (100 ng/ml) or IL-$1{\beta}$(10 ng/ml) to induce chemokines and adhesion molecules involved in eosinophil chemotaxis. Then after treatment of Fructus Liquidambaris, inhibition effect assay such as ELISA, real-time RT-PCR, and chemotaxis assay was performed. Results: Eotaxin level was suppressed in both protein secretion and mRNA expression. Eosinophil recruitment to lung epithelial cells was also reduced by Fructus Liquidambaris, implying the role of eotaxin in eosinophil recruitment. In addition, expression of IL-8 was also suppressed by Fructus Liquidambaris (p<0.05). However, expression of adhesion molecules (ICAM-1, VCAM-1) related to eosinophil was not affected. The eosinophil migration was inhibited at high concentration of Fructus Liquidambaris (p<0.05). Conclusion: These results suggest that Fructus Liquidambaris may regulate a common signaling pathway of eotaxin and IL-8. FS might be of therapeutic value in diseases such as asthma.