This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Do, Y. Articles by Nagarkatti, M. Search for Related Content PubMed PubMed Citation Articles by Do, Y. Articles by Nagarkatti, M.

Bryostatin-1 Enhances the Maturation and Antigen-Presenting Ability of Murine and Human Dendritic Cells

Departments of ¹ Microbiology and Immunology and ² Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia

In this study, we investigated the effect of bryostatin-1 (Bryo-1), an antineoplastic agent, on dendritic cell (DC) maturation, activation, and functions. Murine bone marrow-derived DCs on culture with Bryo-1 alone, Bryo-1 + calcium ionophore (CI), but not CI alone exhibited morphologic changes characteristic of mature DCs and expressed increased levels of CD40, CD80, and CD86. Moreover, Bryo-1 + CI–treated DCs exhibited enhanced antigen-presenting ability to naive and antigen-specific T cells and alloreactive T cells. Bryo-1 + CI–mediated activation of DCs involved protein kinase C (PKC), especially PKC-, -, and -, and addition of PKC inhibitors impaired their ability to activate T cells. Bryo-1 + CI treatment of DCs did not activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase, p38 MAPK, or stress-activated protein kinase/c-Jun NH₂-terminal kinase pathways. Finally, treatment of DCs with Bryo-1 alone and Bryo-1 + CI, but not CI alone, induced nuclear translocation of nuclear factor B as studied by confocal microscopy. DCs generated from human peripheral blood monocytes or from human cord blood CD34⁺ hematopoietic stem cells, when cultured with Bryo-1 + CI, also showed maturation and increased T-cell stimulatory activity. Bryo-1 + CI was more potent in inducing maturation and activation of DCs when compared with other agents such as tumor necrosis factor , lipopolysaccharide, or phorbol 12-myristate 13acetate + CI. Collectively, the current study shows for the first time that Bryo-1 alone or in combination with CI may promote the maturation of DCs and therefore may be useful in development of DC-based cancer immunotherapy.

This article has been cited by other articles:

				N. P. Singh, M. Nagarkatti, and P. Nagarkatti Primary Peripheral T Cells Become Susceptible to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Mediated Apoptosis in Vitro upon Activation and in the Presence of Dendritic Cells Mol. Pharmacol., June 1, 2008; 73(6): 1722 - 1735. [Abstract] [Full Text] [PDF]

				M. Majewski, T. O. Bose, F. C. M. Sille, A. M. Pollington, E. Fiebiger, and M. Boes Protein kinase C delta stimulates antigen presentation by Class II MHC in murine dendritic cells Int. Immunol., June 1, 2007; 19(6): 719 - 732. [Abstract] [Full Text] [PDF]

				J. M. Challacombe, A. Suhrbier, P. G. Parsons, B. Jones, P. Hampson, D. Kavanagh, G. E. Rainger, M. Morris, J. M. Lord, T. T. T. Le, et al. Neutrophils Are a Key Component of the Antitumor Efficacy of Topical Chemotherapy with Ingenol-3-Angelate J. Immunol., December 1, 2006; 177(11): 8123 - 8132. [Abstract] [Full Text] [PDF]

				H. Li, W. Wojciechowski, C. Dell'Agnola, N. E. Lopez, and I. Espinoza-Delgado IFN-{gamma} and T-bet Expression in Human Dendritic Cells from Normal Donors and Cancer Patients Is Controlled through Mechanisms Involving ERK-1/2-Dependent and IL-12-Independent Pathways J. Immunol., September 15, 2006; 177(6): 3554 - 3563. [Abstract] [Full Text] [PDF]

				C. Canetti, D. M. Aronoff, M. Choe, N. Flamand, S. Wettlaufer, G. B. Toews, G.-H. Chen, and M. Peters-Golden Differential regulation by leukotrienes and calcium of Fc{gamma} receptor-induced phagocytosis and Syk activation in dendritic cells versus macrophages J. Leukoc. Biol., June 1, 2006; 79(6): 1234 - 1241. [Abstract] [Full Text] [PDF]

				P. J. Cejas, L. M. Carlson, J. Zhang, S. Padmanabhan, D. Kolonias, I. Lindner, S. Haley, L. H. Boise, and K. P. Lee Protein Kinase C {beta}II Plays an Essential Role in Dendritic Cell Differentiation and Autoregulates Its Own Expression J. Biol. Chem., August 5, 2005; 280(31): 28412 - 28423. [Abstract] [Full Text] [PDF]