title: Prostaglandin E2 is a major soluble factor produced by stromal cells for preventing inflammatory cytokine production from dendritic cells.
abstract: Dendritic cells (DCs) are specialized antigen-presenting cells that play pivotal roles in initiating immune responses. However, DC maturation is usually strongly restricted by the stromal microenvironment, especially in non-lymphoid tissues, such as skin and mucosa. Although suppression of DC maturation by stromal cells has been well documented, the molecular basis of this suppression has not been established. In this study, we examined the role of fibroblasts for DC maturation in vitro. The mouse embryonic fibroblasts (MEFs) strongly suppressed LPS-induced DC maturation. Although suppression of class II MHC and CD40 required DC-MEF contact, soluble factors in the culture supernatant of MEFs were sufficient for the suppression of IL-12 and tumor necrosis factor-alpha production. Using molecular-size selection and HPLC, we determined that prostaglandin E2 (PGE2) is a major soluble inhibitory factor secreted by MEFs. This was confirmed by the fact that cyclooxygenase inhibitors inhibited the production of the suppressive factor by MEFs. These results suggest that PGE2 is a major soluble factor produced by MEFs for the suppression of inflammatory cytokine production from DCs, while a contact mechanism between MEFs and DCs is required for the suppression to induce T cell-stimulating molecules.
authors.affiliation: Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiraishi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kazuko
authors.initials: K
authors.lastname: Saeki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miura
authors.forename: Satoko
authors.initials: S
authors.lastname: Watanabe
authors.forename: Takuma
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Giichi
authors.initials: G
authors.lastname: Takaesu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D012995:Solubility; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D015232:Dinoprostone