Inducible Nitric Oxide Synthase Is Increased in Murine Lung Epithelial Cells by Cytokine Stimulation

• Published in: Biochemical and biophysical research communications Vol. 198; no. 3; pp. 835 - 843
• Main Authors: Robbins, R.A., Springall, D.R., Warren, J.B., Kwon, O.J., Buttery, L.D.K., Wilson, A.J., Adcock, I.M., Riverosmoreno, V., Moncada, S., Polak, J., Barnes, P.J.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.02.1994; Elsevier
• Subjects: Amino Acid Oxidoreductases - biosynthesis; Amino Acid Oxidoreductases - drug effects; Animals; Arginine - analogs & derivatives; Arginine - metabolism; Arginine - pharmacology; Biological and medical sciences; Cell Line; Cell physiology; Citrulline - metabolism; Cytokines - pharmacology; Dexamethasone - pharmacology; Enzyme Induction; Epithelium - drug effects; Epithelium - enzymology; Fundamental and applied biological sciences. Psychology; Guanidines - pharmacology; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Kinetics; Lung - drug effects; Lung - enzymology; Mice; Molecular and cellular biology; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitrites - metabolism; Recombinant Proteins - pharmacology; Responses to growth factors, tumor promotors, other factors; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Corticosteroid; Enzyme; Lung; Rodentia; Cytokine; Gene expression; Nitric-oxide synthase; Signal transduction; Vertebrata; Mammalia; Cell line; Mouse; Nitrogen monoxide; Epithelial cell; Oxidoreductases; Mechanism of action
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1994.1119

Nitric oxide (NO) is detectable in exhaled air. To elucidate whether airway epithelial cells could be a source of NO, we investigated the expression of inducible nitric oxide synthase (iNOS) by the murine lung epithelial cell line, LA-4, in response to cytokine stimulation and the ability of corticosteroids to modulate this effect. Stimulation with cytomix, a combination of interleukin-1β, tumor necrosis factor-α, and interferon-gamma, elevated nitrite levels by 873% in the culture supernatants and enhanced the conversion of arginine to citrulline by 273% at 24 h. An increased number of cells stained for iNOS and an increase in iNOS mRNA was also observed. Dexamethasone decreased the cytokine-induced increase in nitrite levels, NOS activity, iNOS immunoreactivity, and mRNA but did not change the half life of iNOS mRNA. These results show that lung epithelial cells can release NO, a process which can be inhibited by dexamethasone.