Premium
Preconditioning of Endothelial Cells (HUVEC) with Carbon Monoxide (CO) Liberated by CO‐releasing Molecules (CORM) Attenuates LPS‐induced Activation of HUVEC
Author(s) -
Sun Bing Wei,
Katada Kazuhiro,
Bihari Aurelia,
Forbes Tom L.,
Potter Richard F.,
Cepinskas Gediminas
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1390-a
Recently, it has been shown that carbon monoxide (CO), one of the products of inducible heme oxygenase (HO‐1) action on heme suppresses inflammatory response elicited by LPS. However, the mechanism(s) of this phenomenon remain poorly investigated. The aim of this study was to assess the effects and potential mechanisms of CORM‐liberated CO on LPS‐induced activation of endothelial cells (HUVEC). To this end HUVEC were pretreated with tricarbonyldichlororuthenium (II) dimmer (CORM‐2) at the concentration of 10, 50, 100, or 200 μM for 2 hrs, washed and stimulated with LPS (10μg/ml) for additional 4 hrs. Activation (oxidative stress) of HUVEC was assessed by measuring intracellular oxidation of DHR 123 or nitration of DAF‐FM, specific H 2 O 2 and NO fluorochromes, respectively. In addition, the expression of HO‐1 and iNOS protein (Western blot) and activation of inflammation‐relevant transcription factor, NFκB (EMSA) were also assessed. The obtained data indicate that pretreatment of HUVEC with CORM‐2 results in: 1) inhibition of LPS‐induced production of ROS and NO, 2) LPS‐induced activation of NFκB and 3) up‐regulation of HO‐1 but decrease in iNOS at the protein levels. Taken together, the results of this study suggest that CO liberated by CORM‐2 elicits its anti‐inflammatory effects by interfering with the induction of intracellular oxidative stress. In addition, it also supports the notion that CO is a potent inhibitor of iNOS (HSFO‐NA5580 and MOP‐68848).