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

• Main Authors: Zhe Meng, Chao Yan, Qian Deng, Xin Dong, Zong-Ming Duan, Deng-Feng Gao, Xiao-Lin Niu
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2013-06-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Toll-like receptor 4; Oxidized low-density lipoprotein; Mast cells; Inflammatory responses
• Online Access: http://www.karger.com/Article/FullText/350102

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-κB (NF-κB), a critical mediator of inflammation. The expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a) and interleukin 6 (IL-6) was measured subsequently. Results: Ox-LDL increased the expression of TLR4 and secretion of MCP-1, TNF-a and IL-6. Moreover, ox-LDL stimulated the translocation of NF-κB, 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-κB nuclear translocation and phosphorylation of MAPKs, a process mediated in part by TLR4.