Expression and Regulation of Inducible Nitric Oxide Synthase from Human Primary Airway Epithelial Cells

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Abstract
Elevated levels of exhaled nitric oxide are seen in inflammatory airway diseases such as asthma, but the cellular source remains unknown. This study investigated whether human airway epithelial cells express inducible nitric oxide synthase (iNOS). Human bronchial epithelial cells stimulated with 50 ng/ml interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma express iNOS mRNA, protein and increased nitrite in the cell culture media, which was inhibited by the selective iNOS inhibitor 1400W. Cells derived from subjects with asthma produced less nitrite than cells from normal subjects (6.59 +/- 0.99 microM nitrite, n = 15 versus 3.89 +/- 0.42 microM nitrite, n = 20; P < 0.05). This was not attributed to steroid treatment of subjects with asthma because there was no difference in the amount of nitrite released from steroid-naive and steroid-treated cells (3.51 +/- 0.46 versus 4.27 +/- 0.7 microM nitrite, n = 10). Neither dexamethasone nor budesonide inhibited iNOS mRNA induction, protein expression, or nitrite accumulation. The cells were not steroid insensitive because steroids inhibited GM-CSF release. Therefore, although these cells express iNOS under inflammatory conditions, they do not appear to be regulated directly by glucocorticosteroids.