The induction of cytokine release in monocytes by electronegative low-density lipoprotein (LDL) is related to its higher ceramide content than native LDL

Montserrat Estruch, Jose Luis Sanchez-Quesada, Lorea Beloki, Jordi Ordoñez-Llanos, Sonia Benitez

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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. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
Original languageEnglish
Pages (from-to)2601-2616
JournalInternational Journal of Molecular Sciences
Volume14
Issue number2
DOIs
Publication statusPublished - 1 Feb 2013

Keywords

  • Ceramide
  • Cytokines
  • Diacylglycerol
  • Electronegative LDL
  • HDL
  • Lipoprotein aggregation
  • Monocytes
  • Phospholipase C

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    Estruch, M., Sanchez-Quesada, J. L., Beloki, L., Ordoñez-Llanos, J., & Benitez, S. (2013). The induction of cytokine release in monocytes by electronegative low-density lipoprotein (LDL) is related to its higher ceramide content than native LDL. International Journal of Molecular Sciences, 14(2), 2601-2616. https://doi.org/10.3390/ijms14022601