Unconjugated bilirubin modulates nitric oxide production via iNOS regulation.
To induce the in vitro endothelial dysfunction model, H5V cells were treated with tumor necrosis factor α (TNFα) and with unconjugated bilirubin (UCB) at two different physiological concentrations. The TNFα-induced reduction of nitric oxide (NO) concentration was reversed by UCB. Endothelial NO synthase (eNOS) gene expression was not influenced by treatments while inducible NO synthase (iNOS) expression was increased at 24 h. Co-treatment of H5V cells with pyrrolidine dithiocarbamate, TNFα (20 ng/mL) and UCB (Bf 15 or 30 nM) for 2 h caused a significant reduction of iNOS gene expression. We conclude that at physiological concentrations UCB prevents endothelial dysfunction by modulating NO concentration probably through inhibition of NF-κB.
Centro Studi Fegato, Fondazione Italiana Fegato, AREA Science Park, Campus Basovizza Trieste, Italy.
Graciela L
GL
Mazzone
Igino
I
Rigato
Claudio
C
Tiribelli
D000704:Analysis of Variance; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011759:Pyrrolidines; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D009573:Nitrites; D011759:Pyrrolidines; D013778:Tetrazolium Salts; D013844:Thiazoles; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C022616:thiazolyl blue; D001663:Bilirubin