LPS induces CXCL16 expression in HUVECs through the miR-146a-mediated TLR4 pathway

Endothelial inflammation characterizes the early stages of atherosclerosis. CXCL16 is a protein that functions as both a chemokine and adhesion molecule, playing a crucial role in the pathogenesis of atherosclerosis. However, it is uncertain if LPS, a major inducer of inflammation, affects CXCL16 expression in endothelial cells and whether miR-146a, a negative regulator of atherosclerosis, participates in this process. The present study showed that exposure of human umbilical vein endothelial cells (HUVECs) to LPS induced the overexpression of CXCL16, TLR4 and NF-kappa B, and this induction was blocked by the TLR4 inhibitor TAK-242. In addition, LPS induced the upregulation of miR-146a in HUVECs. Overexpression or inhibition of miR-146a either inhibited or increased the LPS-induced expression CXCL16, TLR4 and NF-kappa B protein production, respectively. Additionally, miR-146a-induced CXCL16 expression was blocked by TAK-242. Thus, in this study, we demonstrate that LPS stimulates CXCL16 expression via the TLR4/NF-kappa B signaling pathway, and simultaneously, miR-146 negatively regulates LPS-induced CXCL16 expression through a TLR4-dependent mechanism.