کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6002336 | 1182967 | 2014 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: oxLDL/β2GPI/anti-β2GPI complex induced macrophage differentiation to foam cell involving TLR4/NF-kappa B signal transduction pathway oxLDL/β2GPI/anti-β2GPI complex induced macrophage differentiation to foam cell involving TLR4/NF-kappa B signal transduction pathway](/preview/png/6002336.png)
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.
Journal: Thrombosis Research - Volume 134, Issue 2, August 2014, Pages 384-392