• Environmental Analysis Health and Toxicology
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• 제21권4호
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• pp.357-363
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• 2006

Chromium compounds are widely used in diverse industries including pigment manufacturing, painting, metal plating and leather tanning. With the wide uses of chromium, various adverse effects of the compounds on the environment and human health have been reported. Among them, hexavalent chromium [Cr (VI)], which is a carcinogenic heavy metal, has been widely studies. Epidemiological investigations have shown that respiratory cancers had been found in workers who had been occupationally exposed to Cr (VI). In this study, cell toxicity and induction of reactive oxygen species (ROS) by Cr (VI) (1, 2, 4, $8{\mu}M$) in cultured human bronchial epithelial cells were investigated. Exposure of the cells to Cr (VI) led to cell death, ROS increase, and cytosolic caspase-3 activation. The ROS increase was related with the decreased level of GSH. Chromatin condensation and fragmentation were occurred by Cr (VI) when evaluated by DAPI staining or agarose gel electrophoresis of the extracted DNA. Expression of ROS related genes including glutathione S-transferase, heme oxygenase-1, metallothionein were significantly induced in Cr (VI) treated cells. This result suggests the toxicity in cultured cells by Cr (VI) was expressed through the apoptotic process with ROS induction.

• 대한한의학회지
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• 제24권1호
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• pp.74-83
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Socheongryong-tang and Socheongryong-tang plus Sasam (Adenophorae Radix) on the mRNA expressions of Interleukin (IL)-6, IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) involved in the asthma model. Materials and Methods : In this study, BEAS-2B cell lines, human epithelial cells, were used. These cells were stimulated by tumor necrosis factor $(TNF)-{\alpha},{\;}IL-1{\beta}$ and histamine for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for the internal standard. After each 24 hours of the Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑 龍湯加沙蔘) treatment, total cellular RNAs were collected by applying RNAzol directly to the living cells. Then the transcriptional activities of IL-6, IL-8 and GM-CSF were measured by RT-PCR with electrophoresis. Results : In the Socheongryong-tang (小靑龍湯) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). In the Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). Conclusions : This study shows that Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) have dose-dependent inhibitory effects on the mRNA expressions of IL-6, IL-8 and GM-CSF in human epithelial cells, so these herbal medicines may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in the asthma model.

• 대한한의학회지
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• 제24권3호
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• pp.145-154
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Lonicerae Flos and Paeoniae Radix on the mRNA expression of IL-6, IL-16, and GM-CSF involved in the asthma model. Materials and Methods : In the study BEAS-2B cell lines, human epithelial cells were used. These cells were stimulated with tumor necrosis factor $(TNF)-\alpha$ for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for internal standard. After 24 hours of Lonicerae Flos, Paeoniae Radix, total cellular RNAs were collected treating RNA zol directly on the living cells. Then the transcriptional activities of IL-6, 16, GM-CSF were measured by RT- PCR with electrophoresis. Results : In the Lonicerae Flos study, the mRNA expression of IL-6, IL-16 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. In the Paeoniae Radix study, the mRNA expression of IL-6, IL-l6 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. Conclusion : This study shows that Lonicerae Flus and Paeuniae Radix have no inhibitory effects on the mRNA expression of IL-6, IL-16 and GM-CSF in BEAS-2B cell lines, human epithelial cells. Advanced studies are required to investigate the other mechanisms of inhibitory effect by Lonicerae Flus and Paeoniae Radix in the asthma model.

• Toxicological Research
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• 제21권4호
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• pp.303-307
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• 2005

Nanomaterials, which ranges in size from 1 to 100 nm, have been used to create uqnique devices at the nanoscale level possessing novel physical and chemical functional properties. However, the toxicities of nanomaterials have not been fully tested and the risk of nanomaterials is emerging issues in these days. In this study, the cytotoxicity of copper nanoparticles was tested in cultured human bronchial epithelial cells. As a results, copper nanoparticles showed cytotoxicity similar with cupric ion and the apoptotic mechanisms of DNA fragmentation and caspase-3 activation were involved. Induction of heme oxygenase-1 and thioredoxin reductase by copper nanoparticles indicated that cytotoxicity of copper nanoparticles is likely to be mediated through oxidative stress.

• Journal of Acupuncture Research
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• 제22권1호
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• pp.155-164
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• 2005

사람 기관지 상피세포에 알러지 환경을 유발 하고자 사이토카인을 처리하여 TARC의 분비를 유도하고, 이 케모카인 분비에 반하(半夏) 약쇄액(藥鎖液)이 미치는 효과를 실험한 결과 다음과 같은 결론을 얻었다. 1. 사람의 기관지 상피 세포주에 각각 IL-4, TNF-${\alpha}$, IFN-${\gamma}$ 및 IL-$1{\beta}$를 처리하는 경우와 IL-4와 TNF-${\alpha}$, INF-${\alpha}$와 IFN-${\gamma}$, IFN-${\gamma}$와 IL-$1{\beta}$를 병용 처리할 경우 TARC의 분비량를 측정한 결과 IL-4와 TNF-${\alpha}$와 TNF-${\alpha}$와 IFN-${\gamma}$를 병용 처리하였을 경우 TARC의 분비량이 유의하게 증가하였다. 2. 반하(半夏) 약쇄액(藥鎖液) 처리군의 24시간 및 48시간에서 통계적으로 유의한 감소를 관찰할 수 있었다. 3. 반하(半夏) 약쇄액(藥鎖液)에 의한 TARC 분비억제를 관찰 한 결과 농도의존적인 분비 감소 효과를 관찰 할 수 있었다. 4. MTT assay법을 이용한 세포 독성 측정에선 대조군과 반하(半夏) 약침액(藥鍼液) 처리군간에 유의성이 없었으므로 50, 100 및 200${\mu}g/m{\ell}$의 농도에선 세포독성이 없었음을 관찰할 수 있었다. 이에 반하(半夏) 약광액(藥鑛液)은 TARC 케모카인 억제를 통해 천식에 대한 치료효과를 나타낼 수 있을 것으로 사려된다.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.836-843
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• 2004

Nontypeable H. influenzae (NTHi), a Gram-negative obligate human pathogen, causes pneumonia, chronic bronchitis, and otitis media, and the respiratory epithelium is the first line of defense that copes with the pathogen. In an effort to identify transcriptional responses of human respiratory epithelial cells to infection with NTHi, we examined its differential gene expression using high density cDNA microarrays. BEAS-2B human bronchial epithelial cells were exposed to NTHi for 3 hand 24 h, and the alteration of mRNA expression was analyzed using microarrays consisting of 8,170 human cDNA clones. The results indicated that approximately 2.6% of the genes present on the microarrays increased in expression over 2-fold and 3.8% of the genes decreased during the 24-h infection period. Upregulated genes included cytokines (granulocyte-macrophage colony stimulating factor 2, granulocyte chemotactic protein 2, IL-6, IL-10, IL-8), transcription factors (Kruppel-like factor 7, CCAAT/enhancer binding protein $\beta$, E2F-1, NF-$\kappa$B, cell surface molecules (CD74, ICAM-1, ICAM-2, HLA class I), as well as those involved in signal transduction and cellular transport. Selected genes were further confirmed by reverse-transcription-PCR. These data expand our knowledge of host cellular responses during NTHi infection and should provide a molecular basis for the study of host-NTHi interaction.

• Biomolecules & Therapeutics
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• 제30권2호
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• pp.170-178
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• 2022

The airway epithelium is equipped with the ability to resist respiratory disease development and airway damage, including the migration of airway epithelial cells and the activation of TLR3, which recognizes double-stranded (ds) RNA. Primary cilia on airway epithelial cells are involved in the cell cycle and cell differentiation and repair. In this study, we used Beas-2B human bronchial epithelial cells to investigate the effects of the TLR3 agonist polyinosinic:polycytidylic acid [Poly(I:C)] on airway cell migration and primary cilia (PC) formation. PC formation increased in cells incubated under serum deprivation. Migration was faster in Beas-2B cells pretreated with Poly(I:C) than in control cells, as judged by a wound healing assay, single-cell path tracking, and a Transwell migration assay. No changes in cell migration were observed when the cells were incubated in conditioned medium from Poly(I:C)-treated cells. PC formation was enhanced by Poly(I:C) treatment, but was reduced when the cells were exposed to the ciliogenesis inhibitor ciliobrevin A (CilioA). The inhibition of Beas-2B cell migration by CilioA was also assessed and a slight decrease in ciliogenesis was detected in SARS-CoV-2 spike protein (SP)-treated Beas-2B cells overexpressing ACE2 compared to control cells. Cell migration was decreased by SP but restored by Poly(I:C) treatment. Taken together, our results demonstrate that impaired migration by SP-treated cells can be attenuated by Poly(I:C) treatment, thus increasing airway cell migration through the regulation of ciliogenesis.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.222-230
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• 2007

Some drugs may be limited in their clinical application due to their propensity towards their adverse effects. Toxicogenomic technology represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process. Nitrofurantoin (NF) is clinical chemotherapeutic agent and antimicrobial and used to treatment of urinary tract infections. However, NF has been shown to result in pulmonary toxic effects. In this research, we revealed the changing expression gene profiles in BEAS-2B, human bronchial epithelial cell line, exposed to NF by using human oligonucleotide chip. Through the clustering analysis of gene expression profiles, we identified 136 up-regulated genes and 379 down-regulated genes changed by more than 2-fold by NF. This study identifies several interesting targets and functions in relation to NF-induced toxicity through a gene ontology analysis method including biological process, cellular components, molecular function and KEGG pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제26권4호
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• pp.239-253
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• 2022

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

• Tuberculosis and Respiratory Diseases
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• 제41권2호
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• pp.73-86
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• 1994

In addition to classic cholinergic and adrenergic pathways, the existence of a third division of autonomic control in the human airways has been proved. It is called a nonadrenergic noncholinergic(NANC) nervous system, and difficult to study in the absence of specific blockers. Neuropeptides are certainly suggested to be transmitters of this NANC nervous system. It is very frustrating to understand the pathophysiologic role of these peptides in the absence of any specific antagonists. However, further studies of neuropeptides might eventually lead to novel forms of treatment for bronchial asthma. Another study of the interaction between different components of the autonomic nervous system, either in ganglionic neurotransmission or by presynaptic modulation of neurotransmitters at the end-organ will elute neural control in airway disease, particularly in asthma. Studies of how autonomic control may be disordered in airway disease should lead to improvements in clinical management. Epithelial damage due to airway inflammation in asthma may induce bronchial hyperresponsiveness. Axon reflex mechanism is one of possible mechanisms in bronchial hyperresponsiveness. Epithelial damage may expose sensory nerve terminals and C-fiber nrve endings are stimulated by inflammatory mediators. Bi-directional communication between the nerves and mast cells may have important roles in allergic process. The psychological factors and conditioning of allergic reactions is suggested that mast cell activation might be partly regulated by the central nervous system via the peripheral nerves. Studies in animal models, in huamn airways in vitro and in patients with airway disease will uncover the interaction between allergic disease processes and psychologic factors or neural mechainsms.