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International Immunology Advance Access published online on July 17, 2008
International Immunology, doi:10.1093/intimm/dxn078
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Hiroshi Shiraishi1, Hideyuki Yoshida1, Kazuko Saeki1, Yoshiki Miura2, Satoko Watanabe1, Takuma Ishizaki1,3, Masayuki Hashimoto1, Giichi Takaesu1, Takashi Kobayashi1 and Akihiko Yoshimura1,3

1 Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
2 Department of Protein Biochemistry, Institute of Life Science, Kurume University, 2432-3 Aikawa-machi, Kurume, Fukuoka 839-0861, Japan
3 Department of Microbiology and Immunology, Keio University of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan

Correspondence to: Correspondence to: A. Yoshimura; E-mail: yoshimura{at}a6.keio.jp

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.

Keywords: fibroblast, lipid mediators, lipopolysaccharide, stromal cell, Toll-like receptor

Transmitting editor: T. Watanabe

Received 15 April 2008, accepted 19 June 2008.


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