Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

Background/Aims: Tanshinone IIA (Tan IIA) is effective in the treatment of inflammation and atherosclerosis. The adhesion of inflammatory cells to vascular endothelium plays important role in atherogenic processes. This study examined the effects of Tan DA on expression of adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-induced endothelial progenitor cells (EPCs). Methods: EPCs were pretreated with Tan IIA and stimulated with TNF-alpha. Mononuclear cell (MNC) adhesion assay was performed to assess the effects of Tan IIA on TNF-alpha-induced MNC adhesion. Expression of vascular cell adhesion molecule-1 (VCAM-1)/intracellular adhesion molecule-1(ICAM-1) and activation of Nuclear factor kappa B (NF-kappa B) signaling pathway were measured. Results: The results showed that the adhesion of MNCs to TNF-alpha-induced EPCs and expression of VCAM-1/ICAM-1 in EPCs were promoted by TNF-alpha, which were reduced by Tan IIA. TNF-alpha increased the amount of phosphorylation of NF-kappa B, IKB-alpha and IKK alpha/beta in cytosolic fractions and NF-kappa B p65 in nucleus, while Tan IIA reduced its amount. Conclusion: This study demonstrated a novel mechanism for the anti-inflammatory/anti-atherosclerotic activity of Tan IIA, which may involve down-regulation of VCAM-1 and ICAM-1 through partial blockage of TNF-alpha-induced NF-kappa B activation and IKB-alpha phosphorylation by the inhibition of IKK alpha/beta pathway in EPCs. (C) 2016 The Author(s) Published by S. Karger AG, Basel