Granulocyte-colony stimulating factor inhibits inducible nitric oxide synthase gene expression in pulmonary epithelial cells in vitro.
Excessive release of nitric oxide (NO) is most likely a crucial pathophysiological pathway leading to pulmonary dysfunction. Thus, repression of supranormal NO production might be one beneficial mechanism of granulocyte-colony stimulating factor (G-CSF) in inflammatory processes. The aim of this study was to investigate the influence of G-CSF on inducible nitric oxide synthase gene expression in the alveolar epithelial cell line L2. We show that G-CSF suppresses interferon-gamma/tumor necrosis factor-alpha (TNF-alpha) induced inducible nitric oxide synthase gene expression detected as inducible nitric oxide synthase cDNA (cDNA concentration was 633 +/- 38 amol/microg total RNA following 24 h incubation with 100 U/ml interferon-gamma/500 U/ml TNF-alpha, and 440 +/- 14 amol/microg total RNA following 24 h incubation with 250 U/ml G-CSF +/- 100 U/ml interferon-gamma/500 U/ml TNF-alpha, respectively). In addition, application of G-CSF resulted in a decreased synthesis of inducible nitric oxide synthase protein and diminished NO release mediated by the cytokines. The suppression of inducible nitric oxide synthase gene expression in L2 cells by G-CSF may represent a beneficial counterregulatory effect on excessive NO synthesis induced by proinflammatory cytokines in the lung.
Hoffmann
G
G
Department of Physiology I, University of Bonn, Germany.
Schobersberger
W
W
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000998:Antiviral Agents; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D012313:RNA; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase