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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2409-2416. Prepublished online as a Blood First Edition Paper on June 14, 2005; DOI 10.1182/blood-2005-03-0854. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-0854v1 106/7/2409    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chen, X. Articles by Howard, O. M. Z. Search for Related Content PubMed PubMed Citation Articles by Chen, X. Articles by Howard, O. M. Z. Related Collections Immunobiology Immunotherapy Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking Xin Chen, Takaya Murakami, Joost J. Oppenheim, and O. M. Zack Howard From the Basic Research Program, Science Applications International Corporation (SAIC)–Frederick; and Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, MD. 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-12p70 (IL-12p70). 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-3 (MIP-3)/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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Martin, D. L. Kurkowski, A. M. Valentino, and F. Santiago-Schwarz Increased Intracellular, Cell Surface, and Secreted Inducible Heat Shock Protein 70 Responses Are Triggered during the Monocyte to Dendritic Cell (DC) Transition by Cytokines Independently of Heat Stress and Infection and May Positively Regulate DC Growth J. Immunol., July 1, 2009; 183(1): 388 - 399. [Abstract] [Full Text] [PDF] F.-c. Lin, Y. Peng, L. A. Jones, P. H. Verardi, and T. D. Yilma Incorporation of CD40 Ligand into the Envelope of Pseudotyped Single-Cycle Simian Immunodeficiency Viruses Enhances Immunogenicity J. Virol., February 1, 2009; 83(3): 1216 - 1227. [Abstract] [Full Text] [PDF] M.-R. Pan, H.-C. Chang, Y.-C. Wu, C.-C. Huang, and W.-C. Hung Tubocapsanolide A Inhibits Transforming Growth Factor-{beta}-activating Kinase 1 to Suppress NF-{kappa}B-induced CCR7 J. Biol. Chem., January 30, 2009; 284(5): 2746 - 2754. [Abstract] [Full Text] [PDF] A. Vojdani and J. Erde Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: Modulating Tumor Immunity, Autoimmunity and Alloreactive Immunity (III) Evid. Based Complement. Altern. Med., September 1, 2006; 3(3): 309 - 316. [Abstract] [Full Text] [PDF] L. Wang, R. Han, I. Lee, A. S. Hancock, G. Xiong, M. D. Gunn, and W. W. Hancock Permanent Survival of Fully MHC-Mismatched Islet Allografts by Targeting a Single Chemokine Receptor Pathway J. Immunol., November 15, 2005; 175(10): 6311 - 6318. [Abstract] [Full Text] [PDF]

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