Human<i>β</i>-Defensin 3 Reduces TNF-<i><i>α</i></i>-Induced Inflammation and Monocyte Adhesion in Human Umbilical Vein Endothelial Cells

Abstract

The aim of this study was to investigate the role of human β -defensin 3 (hBD3) in the initiation stage of atherosclerosis with human umbilical vein endothelial cells (HUVECs) triggered by tumor necrosis factor- (TNF-)<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>α</mml:mi></mml:mrow></mml:math>. The effects of hBD3 on TNF- α -induced endothelial injury and inflammatory response were evaluated. Our data revealed that first, hBD3 reduced the production of interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF) in HUVECs in a dose-dependent manner. In addition, hBD3 significantly prevented intracellular reactive oxygen species (ROS) production by HUVECs. Second, western blot analysis demonstrated that hBD3 dose-dependently suppressed the protein levels of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF- α -induced HUVECs. As a result, hBD3 inhibited monocyte adhesion to TNF- α -treated endothelial cells. Additionally, hBD3 suppressed TNF- α -induced F-actin reorganization in HUVECs. Third, hBD3 markedly inhibited NF - κ B activation by decreasing the phosphorylation of IKK- α / β , I κ B, and p65 subunit within 30 min. Moreover, the phosphorylation of p38 and c-Jun N-terminal protein kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway were also inhibited by hBD3 in HUVECs. In conclusion, hBD3 exerts anti-inflammatory and antioxidative effects in endothelial cells in response to TNF- α by inhibiting NF - κ B and MAPK signaling.