Prostaglandin E(2) modulation of vascular endothelial growth factor production in murine macrophages.
We have previously shown that dietary (n-3) fatty acids decrease mammary tumor vascularization and PGE(2) production. One possible mechanism may be the modulation of vascular endothelial growth factor (VEGF) production by PGE(2). Macrophages are major producers of VEGF, and thus we assessed the role of PGE(2) in vitro and in vivo on their VEGF production. When added to macrophages, pharmacological (10(-7) M) but not physiological (10(-9) to 10(-11) M) concentrations of PGE(2) increased VEGF mRNA and protein levels. That increased expression was relatively rapid and sustained up to 8 hrs, but declined by 24 hrs. Similarly, dibutryl cAMP increased production of VEGF protein which was completely inhibited by H89. Addition of cAMP-elevating agents further potentiated the production of VEGF by PGE(2). Next, (n-3) and (n-6) fatty acids were added to macrophages in vitro or provided in the diet. Macrophages of mice fed safflower oil (n-6) had 2- to 4-fold greater copy number of VEGF transcripts after lipopolysaccarhide (LPS) stimulation compared to fish oil (n-3). A decreasing trend was seen in LPS-induced VEGF secretion from macrophages in vitro after docosahexaenoic acid or eicosapentaenoic acid incubation compared to arachidonic acid. While pharmacological concentrations of PGE(2) modulate VEGF expression, physiological alterations did not alter VEGF protein production by macrophages.
Mukutmoni
M
M
Department of Cell Biology and Human Anatomy, University of California, Davis, CA 95616-8643, USA.
Hubbard
N E
NE
Erickson
K L
KL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013449:Sulfonamides; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D007546:Isoquinolines; D008222:Lymphokines; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D015056:1-Methyl-3-isobutylxanthine