Dendritic cell differentiation with prostaglandin E results in selective attenuation of the extracellular signal-related kinase pathway and decreased interleukin-23 production.
The balance between interleukin (IL)-12 and IL-23 production by dendritic cells (DCs) is crucial for the induction of appropriate immune responses. In the present study, we examined the effect of prostaglandin E(2) (PGE(2)) treatment of DCs during differentiation on IL-12 and IL-23 production in response to Toll-like receptor (TLR) stimulation. Bone marrow-derived DCs were generated by culturing murine bone marrow cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (cont-DCs) or GM-CSF plus PGE(2) (PG-DCs). Upon TLR stimulation, IL-23 production by PG-DCs was markedly decreased compared with that by cont-DCs. However, no significant difference was detected in IL-12 production between these types of DC. To examine the mechanism underlying the impaired production of IL-23 by PG-DCs, we analysed the activities of extracellular signal-related kinases (ERKs) 1/2, p38 mitogen-activated protein kinase (MAPK), c-jun N-terminal kinases 1/2, Akt, and nuclear factor (NF)-kappaB (p65) in these DCs upon TLR stimulation. The ERK1/2 activity in PG-DCs was significantly lower than that of cont-DCs. No significant differences were detected in the activities of other molecules between cont-DCs and PG-DCs. In addition, treatment of cont-DCs with U0126, a specific inhibitor of the ERK pathway, reduced the TLR-mediated production by the DCs of IL-23 but not IL-12. Thus, DC development in the presence of PGE(2) results in selective attenuation of the ERK pathway. The attenuation of ERK activation appears to be responsible for the decreased IL-23 production by PG-DCs.
Hayashi
Fumie
F
Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Yanagawa
Yoshiki
Y
Onoé
Kazunori
K
Iwabuchi
Kazuya
K
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
D053759:Interleukin-23; D018664:Interleukin-12; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015232:Dinoprostone
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