Dendritic cells express hematopoietic prostaglandin D synthase and function as a source of prostaglandin D2 in the skin.
Prostaglandin D2 (PGD2), an arachidonic acid metabolite, has been implicated in allergic responses. A major source of PGD2 in the skin is mast cells that express hematopoietic PGD synthase (H-PGDS). In this study, we show the expression of H-PGDS in human dendritic cells (DCs) and the regulatory mechanisms by which DCs produce PGD2. We detected H-PGDS in epidermal Langerhans cells, dermal DCs, plasmacytoid DCs, and myeloid DCs. Monocyte-derived DCs rapidly secreted PGD2 when stimulated with the calcium ionophore A23187. More importantly, pretreatment of monocyte-derived DCs with PMA (phorbol 12-myrisate 13-acetate) synergistically enhanced the rapid PGD2 secretion induced by A23187, whereas PMA alone did not induce PGD2 secretion. Lipopolysaccharide (LPS) reduced H-PGDS expression, but interferon-gamma followed by LPS induced significant PGD2 production in a delayed time course at 6 hours. This effect was associated with inhibition of LPS-induced H-PGDS reduction. Interestingly, an irritant compound, SDS, also induced a rapid PGD2 release. PGD2 synergistically enhanced CCL22/macrophage-derived chemokine synthesis in interferon-gamma-treated human keratinocytes. In addition, bone marrow-derived DCs from wild-type mice stimulated lymph node cells to produce higher amounts of interleukin-17 than did DCs from mice lacking the H-PGDS gene. Thus, DCs could be an important source of skin PGD2 and may mediate or regulate skin inflammation by releasing PGD2 in response to various stimuli, contributing to the innate and/or acquired immune responses.
Shimura
Chieko
C
Department of Dermatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Satoh
Takahiro
T
Igawa
Ken
K
Aritake
Kosuke
K
Urade
Yoshihiro
Y
Nakamura
Masataka
M
Yokozeki
Hiroo
H
D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000201:enzymology; D054422:Chemokine CCL22 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D020405:Dermis / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007801:Langerhans Cells / Q000201:enzymology / Q000473:pathology; D054834:Lipocalins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D015230:Prostaglandin D2 / Q000096:biosynthesis* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C515482:CCL22 protein, human; D054422:Chemokine CCL22; D020381:Interleukin-17; D007476:Ionophores; D007509:Irritants; D054834:Lipocalins; D008070:Lipopolysaccharides; D012967:Sodium Dodecyl Sulfate; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2