Endothelial cells secrete triglyceride lipase and phospholipase activities in response to cytokines as a result of endothelial lipase.
The endothelium interacts extensively with lipids and lipoproteins, but there are very few data regarding the ability of endothelial cells to secrete lipases. In this study, we investigated the ability of endothelial cells to secrete the triglyceride lipase and phospholipase activities characteristic of endothelial lipase (EL), a recently described member of the triglyceride lipase gene family. No lipase activities were detected under basal conditions, but treatment with cytokines significantly stimulated the expression of both activities. Using antibodies to EL, we determined that both activities were primarily a result of this enzyme. In addition to the increase in lipolytic activity, cytokine treatment was demonstrated to substantially upregulate EL protein and EL mRNA in a dose-dependent manner. Cytokines did not change EL mRNA stability. Both new protein synthesis and activation of NF-kappaB influenced the induction of EL by cytokines, suggesting that multiple pathways contribute to this process. The upregulation of EL by cytokines is in sharp contrast to the downregulation by cytokines of the other two major members of this gene family, lipoprotein lipase and hepatic lipase, and has implications for the physiological role of EL in inflammatory conditions and its potential role in the modulation of lipoprotein metabolism during inflammatory conditions, including atherosclerosis.
Jin
Weijun
W
Department of Medicine, University of Pennsylvania, Philadelphia, Pa, USA.
Sun
Gwo-Shing
GS
Marchadier
Dawn
D
Octtaviani
Edelyn
E
Glick
Jane M
JM
Rader
Daniel J
DJ
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008833:Microcirculation / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D016207:Cytokines; D007375:Interleukin-1; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D010740:Phospholipases; C410382:LIPG protein, human; D008049:Lipase