Ethanol potentiates lipopolysaccharide- or interleukin-1 beta-induced nitric oxide generation in RBE4 cells.
Our present study investigated the effects of ethanol treatment on inducible nitric oxide (NO) synthase pathway from lipopolysaccharide- or interleukin-1 beta-treated cultured rat blood-brain barrier cell line (rat brain endothelial 4 cells: RBE4 cells). Cells were lipopolysaccharide- or interleukin-1 beta-treated with or without ethanol (50, 100 or 200 mM) for 16 or 24 h. Inducible NO synthase activity and mRNA expression were measured using Griess reaction and reverse transcription-polymerase chain reaction (RT-PCR) respectively. In the absence of lipopolysaccharide or interleukin-1 beta, ethanol treatments failed to stimulate inducible NO synthase gene expression. Lipopolysaccharide or interleukin-1 beta increased nitrite production and inducible NO synthase mRNA levels, and ethanol potentiated this effect. We concluded that ethanol could aggravate the consequences of NO generation by RBE4 cells after inducible NO synthase induction following inflammation or sepsis. This ethanol action on NO generation could contribute to circulatory failure associated with shock due to sepsis or hemorrhage, and alter blood-brain barrier permeability.
INSERM U295, Université de Médecine Pharmacie, Rouvray, France.
M
M
Naassila
F
F
Roux
F
F
Beaugé
M
M
Daoust
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004357:Drug Synergism; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D009573:Nitrites / Q000378:metabolism; D051381:Rats
D007375:Interleukin-1; D008070:Lipopolysaccharides; D009573:Nitrites; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase