Abstract:

Objective  To investigate the influence of the carbon monoxide releasing molecule (CORM) on adhesion molecules, and to test the ability of carbon monoxide (CO) to modulate the expression of vascular cell adhesion molecule (VCAM) under inflammatory conditions. Methods  Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and divided into the HUVEC group, the HUVEC-TNF-α group (culture medium containing 50ng/mL TNF-α) and the HUVEC-TNF-α-CORM-3 group (culture medium containing TNF-α and 1mmoL CORM-3). The influence of CORM-3 on VCAM-1 and hemeoxygenase (HO)-1 expression was assessed by flow cytometry. The nuclear factor (NF)-κB pathway was detected by electrophoretic mobility shift assay. After siRNA was transfected into HUVEC, HO-1 expression was examined by Western blotting. When it was expressed successfully, cells were stimulated with TNF-α in the presence or absence of CORM-3 to evaluate VCAM-1 expression by Western blotting. Results  CORM-3 could inhibit the expression of VCAM-1 on TNF-α-stimulated HUVEC. However, CORM-3 lost all its ability to modulate adhesion molecule when it had released all CO. Still, CORM-3 was able to induce HO-1 expression, but the inhibition of CORM-3 on VCAM-1 expression was not mediated by HO-1. CORM-3 could inhibit TNF-α-induced activation of NF-κB pathway. Conclusion  Down-regulation of VCAM is the important means to inhibit the process of inflammatory response. The regulation of CO on VCAM-1 expression of HUVEC cells stimulated by inflammatory mediators is predominantly achieved by its inhibition on NF-κB activation.

Key words: Carbon monoxide releasing molecule; Vascular cell adhesion molecule; Cell culture in vitro; Hemeoxygenase; Human umbilical vein endothelial cells