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Int. J. Mol. Sci. 2013, 14(2), 2601-2616; doi:10.3390/ijms14022601
Article

The Induction of Cytokine Release in Monocytes by Electronegative Low-Density Lipoprotein (LDL) Is Related to Its Higher Ceramide Content than Native LDL

1,2,* , 1
,
2
,
1,2,3
 and
1,*
1 Cardiovascular Biochemistry Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona 08041, Spain 2 Biochemistry and Molecular Biology Department, Autonomous University of Barcelona, Sant Pau Hospital Unity, Barcelona 08041, Spain 3 Biochemistry Department, Sant Pau Hospital, Barcelona 08041, Spain
* Authors to whom correspondence should be addressed.
Received: 3 December 2012 / Revised: 5 January 2013 / Accepted: 16 January 2013 / Published: 28 January 2013
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
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Abstract

Electronegative low-density lipoprotein (LDL(−)) is a minor modified LDL subfraction that is present in blood. LDL(−) promotes inflammation and is associated with the development of atherosclerosis. We previously reported that the increase of cytokine release promoted by this lipoprotein subfraction in monocytes is counteracted by high-density lipoprotein (HDL). HDL also inhibits a phospholipase C-like activity (PLC-like) intrinsic to LDL(−). The aim of this work was to assess whether the inhibition of the PLC-like activity by HDL could decrease the content of ceramide (CER) and diacylglycerol (DAG) generated in LDL(−). This knowledge would allow us to establish a relationship between these compounds and the inflammatory activity of LDL(−). LDL(−) incubated at 37 °C for 20 h increased its PLC-like activity and, subsequently, the amount of CER and DAG. We found that incubating LDL(−) with HDL decreased both products in LDL(−). Native LDL was modified by lipolysis with PLC or by incubation with CER-enriched or DAG-enriched liposomes. The increase of CER in native LDL significantly increased cytokine release, whereas the enrichment in DAG did not show these inflammatory properties. These data point to CER, a resultant product of the PLC-like activity, as a major determinant of the inflammatory activity induced by LDL(−) in monocytes.
Keywords: electronegative LDL; HDL; cytokines; ceramide; diacylglycerol; lipoprotein aggregation; monocytes; phospholipase C electronegative LDL; HDL; cytokines; ceramide; diacylglycerol; lipoprotein aggregation; monocytes; phospholipase C
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Estruch, M.; Sanchez-Quesada, J.L.; Beloki, L.; Ordoñez-Llanos, J.; Benitez, S. The Induction of Cytokine Release in Monocytes by Electronegative Low-Density Lipoprotein (LDL) Is Related to Its Higher Ceramide Content than Native LDL. Int. J. Mol. Sci. 2013, 14, 2601-2616.

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