Prostaglandin E2 modulation of vascular endothelial growth factor production in murine macrophages

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23 Scopus citations

Abstract

We have previously shown that dietary (n-3) fatty acids decrease mammary tumor vascularization and PGE2 production. One possible mechanism may be the modulation of vascular endothelial growth factor (VEGF) production by PGE2. Macrophages are major producers of VEGF, and thus we assessed the role of PGE2 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 PGE2 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 PGE2. 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 PGE2 modulate VEGF expression, physiological alterations did not alter VEGF protein production by macrophages.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume65
Issue number3
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

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