Prostaglandin E2 is a major soluble factor produced by stromal cells for preventing inflammatory cytokine production from dendritic cells

Hiroshi Shiraishi, Hideyuki Yoshida, Kazuko Saeki, Yoshiki Miura, Satoko Watanabe, Takuma Ishizaki, Masayuki Hashimoto, Giichi Takaesu, Takashi Kobayashi, Akihiko Yoshimura

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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-α 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.

Original languageEnglish
Pages (from-to)1219-1229
Number of pages11
JournalInternational immunology
Volume20
Issue number9
DOIs
Publication statusPublished - 2008 Oct 30

Keywords

  • Fibroblast
  • Lipid mediators
  • Lipopolysaccharide
  • Stromal cell
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Shiraishi, H., Yoshida, H., Saeki, K., Miura, Y., Watanabe, S., Ishizaki, T., Hashimoto, M., Takaesu, G., Kobayashi, T., & Yoshimura, A. (2008). Prostaglandin E2 is a major soluble factor produced by stromal cells for preventing inflammatory cytokine production from dendritic cells. International immunology, 20(9), 1219-1229. https://doi.org/10.1093/intimm/dxn078