Human monocyte-derived dendritic cells are deficient in prostaglandin E2 production.
Monocyte-derived dendritic cells (moDCs) are increasingly used in clinical settings to stimulate tumor immunity. Prostaglandin E2 (PGE2), which is a member of the eicosanoid family of oxygenated arachidonic acid derivatives generated through the action of cyclooxygenases (COXs), is frequently used to enhance the tumor necrosis factor-alpha-induced terminal maturation of moDCs. We show here that one effect of interleukin (IL)-4, which is used together with GM-CSF to generate moDCs, is the suppression of endogenous PGE2 production in moDCs. IL-4 inhibits the cytoplasmic form of phospholipase A2, the enzyme that specifically liberates arachidonic acid from membrane phospholipids. Although moDCs failed to mobilize endogenous arachidonic acid, they converted exogenous arachidonic acid into PGE2 in a COX-1- and COX-2-dependent fashion. IL-4-mediated suppression of PGE2 biosynthesis in human moDCs explains the previously reported maturation-enhancing effect of exogenous PGE2. The general suppression of eicosanoid biosynthesis may, however, limit the immunological efficacy of moDCs generated with IL-4.
Zelle-Rieser
Claudia
C
Department of Urology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Ramoner
Reinhold
R
Artner-Dworzak
Erika
E
Casari
Andrea
A
Bartsch
Georg
G
Thurnher
Martin
M
D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000172:deficiency*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2
D008070:Lipopolysaccharides; D015847:Interleukin-4; D016718:Arachidonic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone