Document Detail


Endogenous nitric oxide limits cytokine-induced damage of murine lung epithelial cells.
MedLine Citation:
PMID:  9142945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study investigated whether endogenous nitric oxide (NO) limits cytokine-induced damage to the murine lung epithelial cell line LA-4. NO production was assessed as nitrite using the Griess reaction, and cell damage was assessed using ethidium homodimer-1. Cytotoxicity was first detected after a 24-h incubation with a combination of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma (cytomix). Nitrite production increased to 78.0 +/- 0.5 nmol/10(6) cells at 24 h. Coincubation of LA-4 with cytomix and NO synthase inhibitors, aminoguanidine (3-1,000 microM) and N(G)-monomethyl-L-arginine (10-1,000 microM), but not N(G)-monomethyl-D-arginine, or a soluble guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one, reduced cytomix-induced nitrite production and increased cytotoxicity up to twofold (24 h). Removal of L-arginine from the medium increased damage; reintroduction of 1,000 microM L-arginine, but not D-arginine, reversed this. In aminoguanidine-treated cells, replacement of NO with an NO donor, S-nitrosoglutathione (30 microM), reversed, in part, the cell damage observed in aminoguanidine/cytomix-treated cells. These results suggest that endogenous NO limits cytokine-induced lung epithelial damage.
Authors:
A Burke-Gaffney; P G Hellewell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  272     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-06-06     Completed Date:  1997-06-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L707-13     Citation Subset:  IM    
Affiliation:
Applied Pharmacology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine / pharmacology
Cytokines / pharmacology*
Drug Combinations
Enzyme Inhibitors / pharmacology
Epithelium / drug effects,  pathology
Ethidium / analogs & derivatives,  pharmacokinetics
Glutathione / analogs & derivatives,  pharmacology
Guanylate Cyclase / antagonists & inhibitors
Interferon-gamma / pharmacology
Interleukin-1 / pharmacology
Lung / drug effects*,  pathology
Mice
Nitric Oxide / physiology*
Nitric Oxide Synthase / antagonists & inhibitors
Nitrites / metabolism
Nitroso Compounds / pharmacology
Oxadiazoles / pharmacology
Quinoxalines / pharmacology
S-Nitrosoglutathione
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / pharmacology
Chemical
Reg. No./Substance:
0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Cytokines; 0/Drug Combinations; 0/Enzyme Inhibitors; 0/Interleukin-1; 0/Nitrites; 0/Nitroso Compounds; 0/Oxadiazoles; 0/Quinoxalines; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 3546-21-2/Ethidium; 57564-91-7/S-Nitrosoglutathione; 61926-22-5/ethidium homodimer; 70-18-8/Glutathione; 74-79-3/Arginine; 82115-62-6/Interferon-gamma; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.6.1.2/Guanylate Cyclase

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