Inducible nitric oxide synthase is increased in murine lung epithelial cells by cytokine stimulation.
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-1 beta, tumor necrosis factor-alpha, 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.
Robbins
R A
RA
Department of Thoracic Medicine, National Heart & Lung Institute, London, U.K.
Springall
D R
DR
Warren
J B
JB
Kwon
O J
OJ
Buttery
L D
LD
Wilson
A J
AJ
Adcock
I M
IM
Riveros-Moreno
V
V
Moncada
S
S
Polak
J
J
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002956:Citrulline / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D006146:Guanidines / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D006146:Guanidines; D007375:Interleukin-1; D009573:Nitrites; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002956:Citrulline; D003907:Dexamethasone; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester