Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells.

• DOI: 10.1073/pnas.91.21.10089
• Publication Date: 2006-05-31T12:57:05Z
• Authors: K Asano; C B Chee; B Gaston; C M Lilly; C Gerard; J M Drazen; J S Stamler
• Keywords: 0301 basic medicine; Lung Neoplasms; Base Sequence; Epidermal Growth Factor; Molecular Sequence Data; Adenocarcinoma; Polymerase Chain Reaction; Epithelium; Gene Expression Regulation, Enzymologic; Cell Line; Pulmonary Alveoli; Interferon-gamma; 03 medical and health sciences; Enzyme Induction; Tumor Cells, Cultured; Cytokines; Humans; Amino Acid Oxidoreductases; Nitric Oxide Synthase; Lung; DNA Primers; Interleukin-1

Histochemical activity and immunoreactivity of nitric oxide synthase (NOS, EC 1.14.13.39) have been recently demonstrated in human lung epithelium. However, the molecular nature NOS regulation function enzyme(s) airway is not known. A549 cells (human alveolar type II epithelium-like), BEAS 2B (transformed bronchial epithelial cells), primary cultures all exhibited constitutive that was calcium dependent inhibitable by inhibitor NG-monomethyl-L-arginine. Nitric production enhanced culture presence interferon gamma, interleukin 1 beta, tumor necrosis factor alpha, lipopolysaccharide; expressed under these conditions showed less dependence on calcium, reminiscent other inducible forms NOS. Two distinct mRNA species, homologous to previously identified brain (type I) hepatic II) NOS, were reverse transcription-polymerase chain reaction cell lines. Northern analysis confirmed expression mRNA. Cell with epidermal growth factor, a principal regulator function, decreased posttranscriptional action but did affect activity. The coexistence consistent complex mechanism evolved protect host from microbial assault at air/surface interface while shielding induction hyperreactivity.