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)-kappaB 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-kappaB 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-kappaB activation.
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)-kappaB 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-kappaB 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-kappaB activation.
Authors: D B Cines; E S Pollak; C A Buck; J Loscalzo; G A Zimmerman; R P McEver; J S Pober; T M Wick; B A Konkle; B S Schwartz; E S Barnathan; K R McCrae; B A Hug; A M Schmidt; D M Stern Journal: Blood Date: 1998-05-15 Impact factor: 22.113
Authors: L E Otterbein; F H Bach; J Alam; M Soares; H Tao Lu; M Wysk; R J Davis; R A Flavell; A M Choi Journal: Nat Med Date: 2000-04 Impact factor: 53.440
Authors: A Yachie; Y Niida; T Wada; N Igarashi; H Kaneda; T Toma; K Ohta; Y Kasahara; S Koizumi Journal: J Clin Invest Date: 1999-01 Impact factor: 14.808
Authors: M L Ferrándiz; N Maicas; I Garcia-Arnandis; M C Terencio; R Motterlini; I Devesa; L A B Joosten; W B van den Berg; M J Alcaraz Journal: Ann Rheum Dis Date: 2007-12-06 Impact factor: 19.103
Authors: Philomena Pullikotil; Hui Chen; Ranganath Muniyappa; Cynthia C Greenberg; Shutong Yang; Chad E N Reiter; Ji-Won Lee; Jay H Chung; Michael J Quon Journal: J Nutr Biochem Date: 2011-12-01 Impact factor: 6.048
Authors: Yingchun Li; Lars Hemmersbach; Bernhard Krause; Nikolay Sitnikov; Anna Schlundt Née Göderz; Diego O Pastene Maldonado; Hans-Günther Schmalz; Benito Yard Journal: Chembiochem Date: 2021-10-26 Impact factor: 3.461
Authors: Charalambos Tsagogiorgas; Johannes Wedel; Maximilia Hottenrott; Michael O Schneider; Uta Binzen; Wolfgang Greffrath; Rolf-Detlef Treede; Bastian Theisinger; Sonja Theisinger; Rüdiger Waldherr; Bernhard K Krämer; Manfred Thiel; Peter Schnuelle; Benito A Yard; Simone Hoeger Journal: PLoS One Date: 2012-08-20 Impact factor: 3.240
Authors: E Stamellou; D Storz; S Botov; E Ntasis; J Wedel; S Sollazzo; B K Krämer; W van Son; M Seelen; H G Schmalz; A Schmidt; M Hafner; B A Yard Journal: Redox Biol Date: 2014-06-05 Impact factor: 11.799