BioScience Trends. 2009;3(4):151-157.

Bilirubin effect on endothelial adhesion molecules expression is mediated by the NF-κB signaling pathway.

Mazzone GL, Rigato I, Ostrow JD, Tiribelli C


We have recently demonstrated that unconjugated bilirubin (UCB) limits the overexpression of adhesion molecules and inhibits the PMN endothelial adhesion induced by the pro-inflammatory cytokine TNFα. To understand the molecular events involved we investigated whether the inhibitory effect is determined by a direct influence of UCB on different nuclear pathways. Co-treatment of cells with UCB, TNFα, and pyrridoline dithiocarbamate (PDTC), a NF-κB inhibitor, additively enhanced the inhibitory effect of UCB. UCB prevented the nuclear translocation of NF-κB induced by TNFα. The failure of UCB to alter TNFα-induced phosphorylation of cAMP-response element-binding protein (CREB) suggested that the CREB pathway is not involved in the UCB inhibition and that UCB blunting effect on the overexpression of adhesion molecules occurs via inhibition of the NF-κB transduction pathway. Collectively these data may contribute to explain the protective effect of bilirubin against development of atherosclerosis.

KEYWORDS: Endothelial cell activation, bilirubin, adhesion molecules, NF-κB, TNFα, atherosclerosis

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