Introduction: Elecronegative LDL (LDL(-)) is a small fraction of the total circulating LDL and has different inflammatory properties, one of the most important being the induction of cytokines in endotelial cells and monocytes. However, the mechanism by which LDL (-) exercises its action at cellular level is not known.The objective of this study was to evaluate the receptors involved in LDL (-) binding in monocytes, and how the liberation of cytokines is induce. Methods: The liberation of MCP1, IL6 and IL10 were evaluated as representative cytokines induced by LDL(-) in monocytes. The production of these cytokines was assessed under baseline conditions, LDL(-) only, and under conditions in which it is inhibited by different receptors using antibodies. Results: It was shown that LDL (-) competes with LPS in the production of cytokines and appears to do this via the toll like receptors (TLR), TLR2 and TLR4 associated with CD14. The results indicate that the proteoglycans (PG) could also play a role, but only in the liberation of MCP1and the CD36 receptor in IL6 release.Monocyte binding studies using fluorescent labeled LDL(-) were performed, which showed that LDL(-) bound to the cells almost as much as LDL(+) as regards the number of particles. In this total binding, neither the PG nor the CD36 could be major entry points, since their block did not affect this binding. On the other hand, the binding of LDL(-) to monocytes was significantly inhibited with anti-CD14 and anti-TLRs antibodies. Conclusion: In conclusion, some of the receptors studied are involved in cytokine induction by LDL(-) in monocytes, among them the TLR-CD14 pathway appears to be important, although the role of this receptor and its involvement in the action of LDL(-) needs to be studied in more detail. © 2010 Elsevier España, S.L. y SEA.
|Journal||Clinica e Investigacion en Arteriosclerosis|
|Publication status||Published - 1 Jul 2010|
- Electronegative LDL
- Toll-like receptors