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Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking
Chen X.; Murakami T.; Oppenheim J.J.; Howard O.M.Z.
2005-10-01
Source PublicationBlood
ISSN00064971 00064971
Volume106Issue:7Pages:2409-2416
Abstract

Triptolide (TPT) is a chemically defined, potent immunosuppressive compound isolated from an anti-inflammatory Chinese herbal medicine. TPT has been reported to inhibit autoimmunity, allograft rejection, and graft-versus-host disease (GVHD), and its efficacy was previously attributed to the suppression of T cells. Since dendritic cells (DCs) play a major role in the initiation of T-cell-mediated immunity, we studied the effects of TPT on the phenotype, function, and migration of human monocyte-derived DCs. TPT treatment, over a pharmacologic concentration range, inhibited the lipopolysaccharide (LPS)-induced phenotypic changes, characteristic of mature DCs and the production of interleukin-12p (IL-12p). Consequently, the allostimulatory functions of DCs were impaired by TPT treatment. Furthermore, the calcium mobilization and chemotactic responses of LPS-stimulated DCs to secondary lymphoid tissue chemokine (SLC)/CC chemokine ligand 21 (CCL21) were significantly lower in TPT-treated than untreated DCs, in association with lower chemokine receptor 7 (CCR7) and higher CCR5 expression. Egress of Langerhans cells (LCs) from explanted mouse skin in response to macrophage inflammatory protein-3β (MIP-3β)/CCL19 was arrested by TPT. In vivo administration of TPT markedly inhibited hapten (fluorescein isothiocyanate [FITC])-stimulated migration of mouse skin LCs to the draining lymph nodes. These data provide new insight into the mechanism of action of TPT and indicate that the inhibition of maturation and trafficking of DCs by TPT contributes to its immunosuppressive effects. © 2005 by The American Society of Hematology.

DOI10.1182/blood-2005-03-0854
URLView the original
Indexed BySCI
WOS Research AreaHematology
WOS SubjectHematology
WOS IDWOS:000232134700036
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Cited Times [WOS]:43   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
AffiliationBasic Research Program, Science Applications International Corporation-Frederick, Inc., Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
Recommended Citation
GB/T 7714
Chen X.,Murakami T.,Oppenheim J.J.,et al. Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking[J]. Blood,2005,106(7):2409-2416.
APA Chen X.,Murakami T.,Oppenheim J.J.,&Howard O.M.Z..(2005).Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking.Blood,106(7),2409-2416.
MLA Chen X.,et al."Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking".Blood 106.7(2005):2409-2416.
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