Oxidized Low-Density Lipoprotein Induces Inflammatory Responses in Cultured Human Mast Cells Via Toll-Like Receptor 4

Background/Aims: Oxidized low-density lipoprotein (ox-LDL) is a powerful atherogen. Toll-like receptor 4 (TLR4) has a pathophysiological role in regulating inflammatory responses and atherosclerosis. Mast cells can infiltrate into the atheromatous plaque and secrete various pro-inflammatory cytokines, which significantly amplify the atherogenic processes and promote plaque vulnerability. Small interfering RNA (siRNA) is an effective method to silence the target genes. We evaluated whether ox-LDL-induced inflammation depended in part on the activation of TLR4-dependent signaling pathways in a cultured human mast cell line (HMC-1). Method: HMC-1 cells were cultured, and treated with ox-LDL, TLR4-specific siRNA, or inhibitors of phosphorylation of mitogen-activated protein kinase (MAPKs), and nuclear factor-kappa B (NF-kappa B), a critical mediator of inflammation. The expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) was measured subsequently. Results: Ox-LDL increased the expression of TLR4 and secretion of MCP-1, TNF-alpha and IL-6. Moreover, ox-LDL stimulated the translocation of NF-kappa B, from the cytoplasm to nucleus. Additionally, phosphorylation of MAPK was greatly increased. These ox-LDL-induced alterations were significantly attenuated by pretreatment with TLR4-specific siRNA. Conclusion: Ox-LDL induced inflammatory responses in cultured HMC-1 cells including NF-kappa B nuclear translocation and phosphorylation of MAPKs, a process mediated in part by TLR4. Copyright (c) 2013 S. Karger AG, Basel.