Triptolide affects the differentiation, maturation and function of human dendritic cells

Triptolide is a purified component from a traditional Chinese herb Tripterygium wilfordii Hook F. It has been shown to have anti-inflammatory and immunosuppressive activities by its inhibitory effect on T cells. But the effect of triptolide on dendritic cells (DC) is unknown. Dexamethasone (Dex) is...

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Veröffentlicht in:International immunopharmacology 2005-08, Vol.5 (9), p.1415-1426
Hauptverfasser: Zhu, Ke-Jian, Shen, Qian-Yun, Cheng, Hao, Mao, Xiao-Hong, Lao, Li-Min, Hao, Guo-Luan
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container_issue 9
container_start_page 1415
container_title International immunopharmacology
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creator Zhu, Ke-Jian
Shen, Qian-Yun
Cheng, Hao
Mao, Xiao-Hong
Lao, Li-Min
Hao, Guo-Luan
description Triptolide is a purified component from a traditional Chinese herb Tripterygium wilfordii Hook F. It has been shown to have anti-inflammatory and immunosuppressive activities by its inhibitory effect on T cells. But the effect of triptolide on dendritic cells (DC) is unknown. Dexamethasone (Dex) is a classic immunosuppressive agent known to suppress the immune response at different levels and has recently found to modulate the development of DC, thereby influencing the initiation of the immune response. In this study, we investigated the affect of triptolide on the differentiation, maturation and function of DC differentiated from human monocytes (MoDC) in vitro in the presence of GM-CSF and IL-4. Dex was included in the study as a reference. Our data show that both triptolide and Dex prevented the differentiation in immature MoDC by inhibiting CD1a, CD40, CD80, CD86 and HLA-DR expression but upregulating CD14 expression, as well as by reducing the capacity of MoDC to stimulate lymphocyte proliferation in the allogeneic mixed lymphocyte reaction. They blocked the maturation of MoDC as totally blocked induction of CD83 expression and absent upregulation of CD40, CD80, CD86 and HLA-DR. In addition, higher concentration of triptolide (20 ng/ml) and 10 − 6 M Dex induced apoptosis in MoDC as measured by expression of APO2.7 and DNA fragmentation (TUNEL assay). However, the phagocytic capacity of MoDC was enhanced by triptolide but not Dex. Therefore, the suppression of DC differentiation, the function in immature DCs as well as the inhibition of DC maturation by triptolide may explain some of its immunosuppressive properties. It is suggested that DCs are a primary target of the immunosuppressive activity of triptolide.
doi_str_mv 10.1016/j.intimp.2005.03.020
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subjects Antigens, CD - metabolism
Apoptosis
Apoptosis - drug effects
Biological and medical sciences
Cell Differentiation - drug effects
Cells, Cultured
Dendritic cell
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dexamethasone - pharmacology
Differentiation
Diterpenes - pharmacology
Endocytic activity
Epoxy Compounds
Humans
Immunosuppressive Agents - pharmacology
Interleukin-10 - metabolism
Interleukin-12 - metabolism
Lymphocyte Culture Test, Mixed
Maturation
Medical sciences
Monocytes - cytology
Monocytes - drug effects
Monocytes - immunology
Pharmacology. Drug treatments
Phenanthrenes - pharmacology
Tripterygium
Triptolide
title Triptolide affects the differentiation, maturation and function of human dendritic cells
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