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Cell Physiol Biochem. 2013;31(6):842-53. doi: 10.1159/000350102. Epub 2013 Jun 7.

Oxidized low-density lipoprotein induces inflammatory responses in cultured human mast cells via Toll-like receptor 4.

Author information

1
Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China. mengzhenihao@163.com

Abstract

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-α (TNF-α) and interleukin 6 (IL-6) was measured subsequently.

RESULTS:

Ox-LDL increased the expression of TLR4 and secretion of MCP-1, TNF-α 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.

PMID:
23816956
DOI:
10.1159/000350102
[Indexed for MEDLINE]
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