TY - JOUR
T1 - The induction of cytokine release in monocytes by electronegative low-density lipoprotein (LDL) is related to its higher ceramide content than native LDL
AU - Estruch, Montserrat
AU - Sanchez-Quesada, Jose Luis
AU - Beloki, Lorea
AU - Ordoñez-Llanos, Jordi
AU - Benitez, Sonia
PY - 2013/2/1
Y1 - 2013/2/1
N2 - 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.
AB - 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.
KW - Ceramide
KW - Cytokines
KW - Diacylglycerol
KW - Electronegative LDL
KW - HDL
KW - Lipoprotein aggregation
KW - Monocytes
KW - Phospholipase C
U2 - 10.3390/ijms14022601
DO - 10.3390/ijms14022601
M3 - Article
VL - 14
SP - 2601
EP - 2616
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 2
ER -