Phospholipase A2-modified low-density lipoprotein activates macrophage peroxisome proliferator-activated receptors

Arteriosclerosis, Thrombosis, and Vascular Biology
Dmitry NamgaladzeBernhard Brüne

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors modulating metabolic and inflammatory responses of phagocytes to stimuli such as fatty acids and their metabolites. We studied the role of PPARs in macrophages exposed to low-density lipoprotein (LDL) modified by secretory phospholipase A(2) (PLA). By analyzing PPAR ligand-binding domain luciferase reporter activation, we observed that PLA-LDL transactivates PPARalpha and PPARdelta, but not PPARgamma. We confirmed that PLA-LDL induced PPAR response element reporter activation by endogenous PPARalpha and PPARdelta in human THP-1 macrophages. By using THP-1 cells with a stable knockdown of PPARalpha and PPARdelta, we showed that PLA-LDL-activated PPARdelta altered macrophage gene expression related to lipid metabolism and lipid droplet formation. Although PPARalpha/delta silencing did not affect cholesterol and triglyceride accumulation in PLA-LDL-treated macrophages, PPARdelta activation by PLA-LDL attenuated macrophage inflammatory gene expression induced by interferon gamma and lipopolysaccharide. PPARdelta activation by PLA-LDL does not influence lipid accumulation in PLA-LDL-treated macrophages. However, it attenuates macrophage in...Continue Reading

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Citations

Mar 30, 2011·Analytical and Bioanalytical Chemistry·Kei YamamotoMakoto Murakami
Jul 13, 2011·Journal of Biochemistry·Makoto MurakamiKei Yamamoto
Mar 1, 2013·Thrombosis and Haemostasis·F CarboneF Montecucco
Sep 17, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Preetha ShridasNancy R Webb
Mar 1, 2012·Cell Biochemistry and Biophysics·Daniel MorbitzerBernhard Brüne
Nov 15, 2011·Free Radical Biology & Medicine·Fiona H GreigCorinne M Spickett

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