Objectives Oxidized low-density lipoprotein (ox-LDL) is a powerful atherogenic factor during atherosclerosis. Toll-like receptor 4 (TLR4) has a pathophysiological role in regulating the inflammatory responses and atherosclerosis. Mast cells can infiltrate in the atheromatous plaque and secrete various pro-inflammatory cytokines, which significantly amplify the atherogenic processes and promote plaque vulnerability. We evaluated whether ox-LDL-induced inflammation depended in part on the activation of TLR4-dependent signalling pathway in cultured human mast cell line (HMC-1).
Methods HMC-1 cells were cultured, and treated with ox-LDL or inhibitors of TLR4, phosphorylation of the mitogen-activated protein kinase (MAPKs), or nuclear factor-κB (NF-κB). The expressions of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) were measured after these treatment.
Results Ox-LDL increased the expression of TLR4 and secretion of MCP-1, TNF-α and IL-6. Moreover, ox-LDL stimulated the transport of NF-κB, a critical mediator of inflammation, from the cytoplasm into nucleus. As well, phosphorylation of the MAPKs pathway was greatly increased. These ox-LDL-induced alterations were significantly attenuated by pretreatment with TLR4-siRNA.
Conclusions Ox-LDL may induce inflammatory responses in cultured HMC-1 cells to cause NF-κB nuclear translocation and phosphorylation of the MAPKs pathway, a process mediated in part by TLR4.