Dexamethasone stimulates transcription of the Na+-K+-ATPase β1gene in adult rat lung epithelial cells

Na+-K+-ATPase plays an essential role in active alveolar epithelial fluid resorption. In fetal and adult alveolar epithelial cells, glucocorticoids (GC) increase Na+-K+-ATPase activity and mRNA levels. We sought to define the mechanism of Na+-K+-ATPase gene upregulation by GC. In a rat alveolar epithelial cell line (RLE), dexamethasone (Dex) increased β1-subunit Na+-K+-ATPase mRNA expression two- to threefold within 3 h after exposure to the GC. The increased gene expression was due to increased transcription as demonstrated by nuclear run-on assays, whereas mRNA stability remained unchanged. Transient transfection of 5′ deletion mutants of a β1promoter-reporter construct demonstrated a 1.5- to 2.2-fold increase in promoter activity by Dex. All of the 5′ deletion constructs contained partial or palindromic GC regulatory elements (GRE) and responded to GC. The increased expression of promoter reporter was inhibited by RU-486, a GC receptor (GR) antagonist, suggesting the involvement of GR. The palindromic GRE at -631 demonstrated Dex induction in a heterologous promoter construct. Gel mobility shift assays using RLE nuclear extracts demonstrated specific binding to this site and the presence of GR. We conclude that GC directly stimulate transcription of Na+-K+-ATPase β1gene expression in adult rat lung epithelial cells through a GR-dependent mechanism that can act at multiple sites.

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Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00165.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. L764-L773 ◽

Cited By ~ 34

Author(s):

Loretta Sparkman ◽

Vijayakumar Boggaram

Keyword(s):

Gene Expression ◽

Nitric Oxide ◽

Protein Kinase ◽

Epithelial Cells ◽

Gene Transcription ◽

Mrna Stability ◽

Inflammatory Responses ◽

Lung Epithelial Cells ◽

Mrna Levels ◽

Lung Epithelial

Interleukin (IL)-8, a C-X-C chemokine, is a potent chemoattractant and an activator for neutrophils, T cells, and other immune cells. The airway and respiratory epithelia play important roles in the initiation and modulation of inflammatory responses via production of cytokines and surfactant. The association between elevated levels of nitric oxide (NO) and IL-8 in acute lung injury associated with sepsis, acute respiratory distress syndrome, respiratory syncytial virus infection in infants, and other inflammatory diseases suggested that NO may play important roles in the control of IL-8 gene expression in the lung. We investigated the role of NO in the control of IL-8 gene expression in H441 lung epithelial cells. We found that a variety of NO donors significantly induced IL-8 mRNA levels, and the increase in IL-8 mRNA was associated with an increase in IL-8 protein. NO induction of IL-8 mRNA was due to increases in IL-8 gene transcription and mRNA stability. NO induction of IL-8 mRNA levels was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823, inhibitors of soluble guanylate cyclase and protein kinase G, respectively, and 8-bromo-cGMP did not increase IL-8 mRNA levels. This indicated that NO induces IL-8 mRNA levels independently of changes in the intracellular cGMP levels. NO induction of IL-8 mRNA was significantly reduced by inhibitors of extracellular regulated kinase and protein kinase C. IL-8 induction by NO was also reduced by hydroxyl radical scavengers such as dimethyl sulfoxide and dimethylthiourea, indicating the involvement of hydroxyl radicals in the induction process. NO induction of IL-8 gene expression could be a significant contributing factor in the initiation and induction of inflammatory response in the respiratory epithelium.

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Upregulation of heme oxygenase gene expression in rat lung epithelial cells following exposure to cadmium

Archives of Toxicology ◽

10.1007/s002040050681 ◽

1999 ◽

Vol 73 (7) ◽

pp. 410-412 ◽

Cited By ~ 6

Author(s):

Hiroki Kitajima ◽

Seishiro Hirano ◽

Kazuo T. Suzuki

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Heme Oxygenase ◽

Lung Epithelial Cells ◽

Rat Lung ◽

Lung Epithelial

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TNF-α inhibits SP-A gene expression in lung epithelial cells via p38 MAPK

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00470.2001 ◽

2002 ◽

Vol 283 (2) ◽

pp. L418-L427 ◽

Cited By ~ 25

Author(s):

Olga L. Miakotina ◽

Jeanne M. Snyder

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

P38 Mapk ◽

Mapk Pathway ◽

Lung Epithelial Cells ◽

Mitogen Activated Protein Kinase ◽

Mrna Levels ◽

Dependent Manner ◽

Tnf Α ◽

Lung Epithelial

Surfactant protein A (SP-A), the major lung surfactant-associated protein, mediates local defense against pathogens and modulates inflammation in the alveolus. Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, inhibits SP-A gene expression in lung epithelial cells. Inhibitors of the phosphatidylinositol 3-kinase pathway, i.e., wortmannin, LY-294002, and rapamycin, did not block the inhibitory effects of TNF-α on SP-A mRNA levels. An inhibitor of the p44/42 mitogen-activated protein kinase (MAPK) pathway, PD-98059, was also ineffective. PD-169316 and SB-203580, inhibitors of p38 MAPK, blocked the TNF-α-mediated inhibition of SP-A mRNA levels. TNF-α increased the phosphorylation of p38 MAPK within 15 min. Anisomycin, an activator of p38 MAPK, increased p38 MAPK phosphorylation and decreased SP-A mRNA levels in a dose-dependent manner. Finally, TNF-α increased the phosphorylation of ATF-2, a transcription factor that is a p38 MAPK substrate. We conclude that TNF-α downregulates SP-A gene expression in lung epithelial cells via the p38 MAPK signal transduction pathway.

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The Severe Acute Respiratory Syndrome Coronavirus 3a Protein Up-Regulates Expression of Fibrinogen in Lung Epithelial Cells

Journal of Virology ◽

10.1128/jvi.79.15.10083-10087.2005 ◽

2005 ◽

Vol 79 (15) ◽

pp. 10083-10087 ◽

Cited By ~ 39

Author(s):

Yee-Joo Tan ◽

Puay-Yoke Tham ◽

Daphne Z. L. Chan ◽

Chih-Fong Chou ◽

Shuo Shen ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cell ◽

Epithelial Cells ◽

Severe Acute Respiratory Syndrome ◽

Cell Line ◽

Pulmonary Complications ◽

Lung Epithelial Cells ◽

Epithelial Cell Line ◽

Mrna Levels ◽

Lung Epithelial

ABSTRACT Here we analyzed the gene expression profile of cells that stably express the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein to determine its effects on host functions. A lung epithelial cell-line, A549, was chosen for this study because the lung is the primary organ infected by SARS-CoV and fatalities resulted mainly from pulmonary complications. Our results showed that the expression of 3a up-regulates the mRNA levels of all three subunits, Aα, Bβ, and γ, of fibrinogen. Consequently, the intracellular levels as well as the secretion of fibrinogen were increased. We also observed increased fibrinogen levels in SARS-CoV-infected Vero E6 cells.

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