TY  - JOUR
A1  - Song, Hui
A1  - Bergstrasser, Claudia
A1  - Rafat, Neysan
A1  - Hoeger, Simone
A1  - Schmidt, Marc
A1  - Endres, N.
A1  - Goebeler, Matthias
A1  - Hillebrands, Jan-Luuk
A1  - Brigelius-Flohé, Regina
A1  - Banning, Antje
A1  - Beck, Grietje
A1  - Loesel, Ralf
A1  - Yard, Benito A.
T1  - The carbon monoxide releasing molecule (CORM-3) inhibits expression of vascular cell adhesion molecule-1 and E- selectin independently of haem oxygenase-1 expression
N2  - Background and purpose: Although carbon monoxide (CO) can modulate inflammatory processes, the influence of CO on adhesion molecules is less clear. This might be due to the limited amount of CO generated by haem degradation. We therefore tested the ability of a CO releasing molecule (CORM-3), used in supra-physiological concentrations, to modulate the expression of vascular cell adhesion molecule (VCAM)-1 and E-selectin on endothelial cells and the mechanism(s) involved. Experimental approach: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumour necrosis factor (TNF)-alpha in the presence or absence of CORM-3. The influence of CORM-3 on VCAM-1 and E- selectin expression and the nuclear factor (NF)-kappa B pathway was assessed by flow cytometry, Western blotting and electrophoretic mobility shift assay. Key results: CORM-3 inhibited the expression of VCAM-1 and E-selectin on TNF-alpha- stimulated HUVEC. VCAM-1 expression was also inhibited when CORM-3 was added 24 h after TNF-alpha stimulation or when TNF-alpha was removed. This was paralleled by deactivation of NF-kappa B and a reduction in VCAM-1 mRNA. Although TNF- alpha removal was more effective in this regard, VCAM-1 protein was down-regulated more rapidly when CORM-3 was added. CORM-3 induced haem oxygenase-1 (HO-1) in a dose- and time-dependent manner, mediated by the transcription factor, Nrf2. CORM-3 was still able to down-regulate VCAM-1 expression in HUVEC transfected with siRNA for HO-1 or Nrf2. Conclusions and implications: Down-regulation of VCAM and E-selectin expression induced by CORM-3 was independent of HO-1 up- regulation and was predominantly due to inhibition of sustained NF-kappa B activation.
Y1  - 2009
UR  - http://www3.interscience.wiley.com/journal/121548564/home
U6  - https://doi.org/10.1111/j.1476-5381.2009.00215.x
SN  - 0007-1188
ER  -