Toll-like receptor 4 promotes macrophage foam cell formation induced by oxidized low-density/β₂-glycoprotein I/β₂-glycoprotein I antibodies complex.
- Author:
Xiaolei ZHANG
1
;
Hong ZHOU
2
;
Ya XU
;
Jingjing LIU
;
Hongxiang XIE
;
Xiangmin KONG
;
Yachao XIE
;
Jinchuan YAN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antigen-Antibody Complex; immunology; Atherosclerosis; immunology; metabolism; Cells, Cultured; Foam Cells; immunology; metabolism; Lipoproteins, LDL; immunology; Macrophages, Peritoneal; immunology; metabolism; Male; Mice; Mice, Inbred C3H; NF-kappa B; metabolism; Thromboplastin; metabolism; Toll-Like Receptor 4; immunology; metabolism; beta 2-Glycoprotein I; immunology
- From: Chinese Journal of Cardiology 2014;42(3):208-213
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the role of toll-like receptor 4 (TLR4) on oxidized low-density/β₂-glycoprotein I/β₂-glycoprotein I (ox-LDL/β₂GPI/anti-β₂GPI) antibodies complex induced macrophage foam cell formation.
METHODSThe peritoneal macrophages were separated from TLR4 intact C3H/HeN mice and TLR4 defective C3H/HeJ mice. The cells were treated with ox-LDL, ox-LDL/β₂GPI, ox-LDL/anti-β₂GPI, anti-β₂GPI/β₂GPI, ox-LDL/β₂GPI/anti-β₂GPI, lipopolysaccharide (LPS) for 48 h and the foam cells were identified by Oil red O staining for intracellular lipids. The total cellular RNA and the protein lysates were collected. The levels of tissue factor (TF) mRNA in two groups were detected by real-time PCR (RT-PCR), and the expression of phosphorylated nuclear factor-κB (NF-κB) p65 was detected by Western blotting. Monocyte chemotactic protein-1 (MCP-1) secretion from peritoneal macrophages was determined by enzyme linked immunosorbent assay (ELISA) kits.
RESULTSCompared with C3H/HeJ mice, lipid droplets in the cytoplasm of peritoneal macrophages from C3H/HeN mice were significantly increased and phosphorylation-NF-κB expression was significantly upregulated after stimulating by ox-LDL/β₂GPI/anti-β₂GPI complex (P < 0.01). TF mRNA and MCP-1 expression were also upregulated post ox-LDL/β₂GPI/anti-β₂GPI complex stimulation [TF mRNA: 0.041 ± 0.023 vs. 0.005 ± 0.003; MCP-1: (6 200.2 ± 6.4) pg/ml vs. (803.3 ± 5.5) pg/ml, P < 0.01].
CONCLUSIONTLR4 can enhance ox-LDL/β₂GPI/anti-β₂GPI complex induced peritoneal macrophage foam cell formation via upregulating phosphorylation-NF-κB, TF and MCP-1 expression.
