Dinoprostone potentiates cytokines and lipopolysaccharides inducing nitric oxide production in cultured rat hepatocytes.
OBJECTIVE
To study the effects of dinoprostone (Din) on nitric oxide (NO) production induced by lipopolysaccharides (LPS) and cytokines mixture (CM) in cultured rat hepatocytes, and the role of cAMP signaling pathway in the induction process.


METHODS
Rat hepatocytes were incubated with indometacin (Ind), Din, forskolin (For), or dibutyryl cyclic GMP (db cGMP) in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24 h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cAMP level was measured with radioimmunoassay.


RESULTS
NO production stimulated by CM was markedly attenuated by Ind in the cultured supernatant, whereas Din and For increased nitrite concentration in the medium. In the presence of CM, both Din and For increased intracellular cAMP level, and had no effect on cAMP level in absence of the stimuli; db cGMP had no influence on the cAMP and NO production both in the presence and absence of same stimuli.


CONCLUSIONS
Din potentiates cytokines and LPS to induce NO production in rat hepatocytes, and the induction may be regulated via intracellular second messenger cAMP signaling pathway.
Zhang
G L
GL
Department of Pharmacology, Beijing Medical University, China. yuankui@public.bta.net.cn
Lin
Z B
ZB
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D008070:Lipopolysaccharides; D005576:Colforsin; D009569:Nitric Oxide; D000242:Cyclic AMP; D015232:Dinoprostone; D007213:Indomethacin