Journal
JOURNAL OF LIPID RESEARCH
Volume 44, Issue 7, Pages 1315-1321Publisher
ELSEVIER
DOI: 10.1194/jlr.M200415-JLR200
Keywords
low density lipoprotein; mitogen-activated; protein kinase; activator protein; macrophages; signal transduction
Categories
Ask authors/readers for more resources
We have previously shown that LDL-containing immune complexes (LDL-ICs) induce up-regulation of LDL receptor (LDLR) expression in human macrophages. The present study further investigated the molecular mechanisms leading to LDLR up-regulation by LDI-ICs as well as the signaling pathways involved. Results showed that treatment of U937 histiocytes with LDL-ICs did not increase the precursors and the cleaved forms of sterol-regulatory element binding proteins (SREBPs) la and 2, suggesting that SREBPs may not be involved in LDLR up-regulation by LDIrICs. Promoter deletion and mutation studies showed that the AP-1 binding sites were essential for LDL-IC-stimulated LDLR expression. Electrophoretic mobility shift assays further demonstrated that LDL-ICs stimulated transcription factor AP-1 activity. Studies assessing the signaling pathways involved in LDLR up-regulation by LDL-ICs showed that the up-regulation of LDLR was extracellular signal-regulated kinase (ERK) dependent. In conclusion, the present study shows that LDL ICs up-regulate LDLR expression via the ERK signaling pathway and the AP-1 motif-dependent transcriptional activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available