Nitric oxide inhibits LPS-induced tumor necrosis factor synthesis in vitro and in vivo.
The effect of nitric oxide (NO) on LPS-stimulated TNF-alpha synthesis has been studied in vitro and in vivo. The synthesis of TNF-alpha in J774 macrophages stimulated with LPS (0.1 microgram/ml) was increased in concentration-related fashion by NO synthase inhibitor L-NMMA (3-30-300 microM) and reduced by either L-arginine (3-30-300 microM) or the NO donor SIN-1 (1-10-100 microM). The level of TNF-alpha in the serum of LPS-challenged rats (6mg/kg/i.p.) was increased in animals pre-treated s.c. with L-NMMA (10 and 50mg/kg) and reduced in those given L-arginine (100 and 300mg/kg). These results show a negative feedback mechanism exhibited by NO on TNF-alpha synthesis suggesting an important regulatory link between NO and TNF-alpha in pathological processes.
Iuvone
T
T
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
D'Acquisto
F
F
Carnuccio
R
R
Di Rosa
M
M
D000818:Animals; D002460:Cell Line; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide