Prostaglandin E2 is a negative regulator on human plasmacytoid dendritic cells.
Prostaglandin E2 (PGE2), a major lipid derived from the metabolism of arachidonic acid, is an environmentally bioactive substance produced by inflammatory processes and acts as a cAMP up-regulator that plays an important role in immune responses. It has been reported that PGE2 has the ability to inhibit the production of interleukin-12 by myeloid dendritic cells (MDCs) and macrophages, and then induce preferential T helper type 2 (Th2) cell responses. However, little is known of the function of PGE2 for plasmacytoid dendritic cells (PDCs), which may contribute to the innate and adaptive immune response to viral infection, allergy and autoimmune diseases. In the present study, we compared the biological effect of PGE2 on human PDCs and MDCs. PGE2 caused the death of PDCs but MDCs survived. Furthermore, we found that, whereas PGE2 inhibited interferon-alpha production by PDCs in response to virus or cytosine-phosphate-guanosine, it inhibited interleukin-12 production by MDCs in response to lipopolysaccharide (LPS) or poly(I:C). Although both virus-stimulated PDCs and LPS-stimulated MDCs preferentially induced the development of interferon-gamma-producing Th1 cells, pretreatment with PGE2 led both DC subsets to attenuate their Th1-inducing capacity. These findings suggest that PGE2 represents a negative regulator on not only MDCs but also PDCs.
Son
Yonsu
Y
The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Ito
Tomoki
T
Ozaki
Yoshio
Y
Tanijiri
Tsutomu
T
Yokoi
Takashi
T
Nakamura
Kengo
K
Takebayashi
Masashi
M
Amakawa
Ryuichi
R
Fukuhara
Shirou
S
D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D003864:Depression, Chemical; D015232:Dinoprostone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000032:analysis / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D007370:Interferon Type I; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D011070:Poly I-C