Humanβ-Defensin 3 Reduces TNF-α-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-) α. 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-κB activation by decreasing the phosphorylation of IKK-α/β, IκB, 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-κB and MAPK signaling.

Sulfur‑containing amino acids in aged garlic extract inhibit inflammation in human gingival epithelial cells by suppressing intercellular adhesion molecule‑1 expression and IL‑6 secretion

“…It has been reported that the hβD3 expression level in gingival tissues and crevicular fluid is decreased in patients with periodontitis in comparison to healthy controls (29). It has been found that hβD3 reduced the level of ICAM-1 protein and inhibits the phosphorylation of NF-κB induced by TNF-α, which is consistent with a finding obtained in HUVECs (26). Although it was not statistically significant, S1PC at 10 µM exhibited near the maximal inhibition induced by S1PC at 100 µM on the elevated ICAM-1 protein by TNF-α (Fig.…”

“…It has been previously demonstrated that the anti-microbial peptide hβD3 reduces the level of TNF-α-elicited ICAM-1 protein in human vein endothelial cells (HUVECs) (26). Thus, this study examined whether the peptide inhibits the level of ICAM-1 protein in Ca9-22 cells.…”

“…Stimulation of the cells with TNF-α has been shown to activate a variety of signaling pathways and transcription factors, such as NF-κB, which plays an essential role in the expression of inflammation-related molecules (26)(27)(28). In addition, hβD3 has been shown to alleviate periodontitis via the suppression of NF-κB (29).…”

Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

“…It is also reported that BDs are capable of electrostatically interacting with negatively charged components in microbial cell walls, by increasing the permeability of cell walls and ultimately leading to a host cell death ( 9 ). In addition to their antimicrobial function, BDs also function as inflammatory mediators, with impact on the immune activation of epithelial cells and immunocytes ( 10 , 11 ), production of inflammatory cytokines ( 12 , 13 ), as well as induction of chemotaxis ( 7 , 14 ). For instance, Beta-defensins 2 (BD2) has been shown to chemoattract immature dendritic cells or memory CD4 + T cells through C–C motif chemokine receptor 6 ( 7 ), while beta-defensins 3 (BD3) and BD4 recruit macrophages dependent on cysteine residues ( 14 ).…”

Human β-defensin 3-combined gold nanoparticles for enhancement of osteogenic differentiation of human periodontal ligament cells in inflammatory microenvironments

“…Furthermore, we observed that AuNPs and hBD3 slightly increased the viability of hPDLCs with the stimulation of E. coli-LPS, which was in agreement with previous reports. 9,22 In addition to the biotoxicity, cellular uptake was another essential component in the cellular response to AuNPs. In this study, 45 nm AuNPs were internalized according to observations of one or two spherical shapes clustered together.…”