Expression of inducible nitric oxide in human lung epithelial cells.
Nitric oxide (NO) is increased in the exhaled air of subjects with several airway disorders. To determine if cytokines could stimulate epithelial cells accounting for the increased NO, the capacity of the proinflammatory cytokines (cytomix: tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma) to increase inducible nitric oxide synthase (iNOS) was investigated in A549 and primary cultures of human bronchial epithelial cells. Cytomix induced a time-dependent increase in nitrite levels in culture supernatant fluids (p < 0.05). Increased numbers of cells stained for iNOS and increased iNOS mRNA was detected in the cytokine-stimulated cells compared to control (p < 0.05). Dexamethasone diminished the cytokine-induced increase in nitrite, iNOS by immunocytochemistry, and iNOS mRNA. These data demonstrate that cytokines, such as those released by mononuclear cells, can induce lung epithelial iNOS expression and NO release, and that this is attenuated by dexamethasone.
Robbins
R A
RA
Department of Thoracic Medicine, National Heart & Lung Institute, London, U.K.
Barnes
P J
PJ
Springall
D R
DR
Warren
J B
JB
Kwon
O J
OJ
Buttery
L D
LD
Wilson
A J
AJ
Geller
D A
DA
Polak
J M
JM
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015152:Blotting, Northern; D001980:Bronchi; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016207:Cytokines; D009573:Nitrites; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester