Granulocyte-colony stimulating factor inhibits inducible nitric oxide synthase gene expression in pulmonary...

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.