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

Abstract:

: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 TNFalpha. 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, TNFalpha, and pyrridoline dithiocarbamate (PDTC), a NF-kappaB inhibitor, additively enhanced the inhibitory effect of UCB. UCB prevented the nuclear translocation of NF-kappaB induced by TNFalpha. The failure of UCB to alter TNFalpha-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-kappaB transduction pathway. Collectively these data may contribute to explain the protective effect of bilirubin against development of atherosclerosis.

journal_name

Biosci Trends

journal_title

Bioscience trends

authors

Mazzone GL,Rigato I,Ostrow JD,Tiribelli C

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

151-7

issue

4

eissn

1881-7815

issn

1881-7823

journal_volume

3

pub_type

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