Epicubenol and Ferruginol induce DC from human monocytes and differentiate IL-10-producing regulatory T cells in vitro.

Abstract

Epicubenol and 19-hydroxyferruginol (Ferruginol) are sesquiterpenes isolated from the black heartwood of Cryptomeria japonica. Dendritic cells (DC) are specialized antigen-presenting cells that monitor the antigenic environment and activate naïve T cells. The role of DC is not only to sense danger but also to tolerize the immune system to antigens encountered in the absence of maturation/inflammatory stimuli. In this study, we attempted to investigate the effects of Epicubenol and Ferruginol on the phenotypic and functional maturation of human monocytes-derived DC in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days under standard conditions, followed by another 2 days with Epicubenol or Ferruginol. The expression levels of CD1a, CD83, and HLA-DR as expressed by mean fluorescence intensity (MFI) on Epicubenol-primed DC or Ferruginol-primed DC were enhanced. Allogeneic Epicubenol-primed DC or Ferruginol-primed DC co-cultured with naïve T cells at 1:5 ratio, secreted IL-10 and TGF-beta, but little IL-4. Moreover, T cells that develop in co-culture of Epicubenol-primed DC or Ferruginol-primed DC and naïve T cells at 1:5 ratio suppressed the proliferation of autologous T cells at Treg cells: Ttarget cells and this suppression of proliferation was inhibited by anti-IL-10 mAb. The expression of FoxP3 mRNA on T cells that develop in co-culture of Epicubenol-primed DC or Ferruginol-primed DC and naïve T cells was lower. From these results, Epicubenol and Ferruginol may induce IL-10-producing Treg 1 cells from naïve T cells by modulating DC function. It seems that Epicubenol and Ferruginol appear to be a target for tolerance after transplantation and in autoimmune diseases.

• Authors: Masao Takei, Akemi Umeyama, Shigenobu Arihara
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 337 Issue 2 Pg. 730-8 (Nov 18 2005) ISSN: 0006-291X [Print] United States
• PMID: 16202980 (Publication Type: Journal Article)

Chemical References

• Abietanes
• Antigens, CD
• Antigens, CD1
• CD1a antigen
• CD83 antigen
• Diterpenes
• FOXP3 protein, human
• Forkhead Transcription Factors
• HLA-DR Antigens
• Immunoglobulins
• Membrane Glycoproteins
• RNA, Messenger
• Sesquiterpenes
• Transforming Growth Factor beta
• epicubenol
• ferruginol
• Interleukin-10
• Interleukin-4
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Abietanes
• Antigens, CD (metabolism)
• Antigens, CD1 (metabolism)
• Cell Differentiation
• Cells, Cultured
• Dendritic Cells (drug effects, metabolism)
• Diterpenes (pharmacology)
• Forkhead Transcription Factors (metabolism)
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• HLA-DR Antigens (metabolism)
• Humans
• Immunoglobulins (metabolism)
• Interleukin-10 (metabolism)
• Interleukin-4 (metabolism)
• Membrane Glycoproteins (metabolism)
• Monocytes (cytology, drug effects)
• Phenotype
• RNA, Messenger (metabolism)
• Sesquiterpenes (pharmacology)
• T-Lymphocytes (metabolism)
• Transforming Growth Factor beta (genetics)