title: oxLDL/β2GPI/anti-β2GPI complex induced macrophage differentiation to foam cell involving TLR4/NF-kappa B signal transduction pathway.
abstract: Macrophage-derived foam cell formation is a hallmark of atherosclerosis. It has been reported that oxidized low density lipoprotein (oxLDL) inducing formation of foam cells and expression of inflammatory molecules are partly mediated by toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway. However, whether oxLDL/β2-glycoprotein I/anti-β2-glycoprotein I (oxLDL/β2GPI/anti-β2GPI) complex enhanced formation of foam cells involving TLR4/NF-κB pathway or not has never been explored. In the current study, we focused on investigating the transformation of peritoneal macrophages from BALB/c mice into foam cells induced by the three complexes, and the involvement of TLR4 as well as its downstream signal molecule NF-κB. The results showed that treatment of macrophages with oxLDL/β2GPI/anti-β2GPI complex could markedly increase intracellular lipid loading and expression of TLR4, phosphorylated NF-κB p65 (p-NF-κB p65), monocyte chemoattractant protein-1 (MCP-1), as well as tissue factor (TF). The oxLDL and oxLDL/β2GPI/anti-β2GPI complex induced formation of foam cells and expression of p-NF-κB p65 were significantly reduced, while macrophages were pre-treated with TLR4 inhibitor TAK-242. Meanwhile, both TAK-242 and NF-κB inhibitor PDTC could remarkably inhibit oxLDL, oxLDL/β2GPI/anti-β2GPI complex, as well as LPS increased MCP-1 and TF levels. Nevertheless, β2GPI/anti-β2GPI complex-induced MCP-1 and TF mRNA expression were inhibited by TAK-242 rather than PDTC, although TF activity was significantly reduced by both of the inhibitors. In conclusion, our results indicate that oxLDL/β2GPI/anti-β2GPI complex could enhance the conversion of macrophages into foam cells and the process may be at least partly mediated by TLR4/NF-κB pathway, which may contribute to the accelerated development of atherosclerosis in APS.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; The First Affiliated Hospital of Soochow University, Suzhou First People's Hospital.
authors.forename: Ya
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: hongzhou@ujs.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: yanjinchuan@hotmail.com.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology; D005487:Foam Cells / Q000166:cytology / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein
keywords: MCP-1; NF-κB; TF; TLR4; foam cell; oxLDL/β2GPI/anti-β2GPI complex