International Immunology Advance Access published online on September 11, 2006
International Immunology, doi:10.1093/intimm/dxl089
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1 The Feinstein Institute for Medical Research, North Shore--LIJ Health System, Manhasset, NY 11030, USA
* To whom correspondence should be addressed. High-mobility group box 1 protein (HMGB1), a DNA-binding nuclear and cytosolic protein, is a pro-inflammatory cytokine released by monocytes and macrophages. HMGB1 as well as its B box domain induce maturation of human dendritic cells (DCs). This report demonstrates that the B box domain induces phenotypic maturation of murine bone marrow-derived dendritic cells (BM-DCs) as evidenced by increased CD86, CD40 and MHC-II expression. The B box domain enhanced secretion of pro-inflammatory cytokines and chemokines: IL-1
Received July 26, 2005
Accepted August 14, 2006
Article
Dendritic cell activating peptides induce distinct cytokine profiles
Gloria Telusma 1, Sandip Datta 2, Ivan Mihajlov 2, Wenxue Ma 3, Jianhua Li 4, Huan Yang 4, Walter Newman 5, Bradley T. Messmer 6, Boris Minev 3, Ingo G. H. Schmidt-Wolf 7, Kevin J. Tracey 4, Nicholas Chiorazzi 6, and Davorka Messmer 8 *
2 Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
3 University of California San Diego, Rebecca and John Moores UCSD Cancer Center, 3855 Health Science Drive, La Jolla, CA 92093, USA
4 The Feinstein Institute for Medical Research, North Shore--LIJ Health System, Manhasset, NY 11030, USA; Department of Surgery, North Shore University Hospital and Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
5 Critical Therapeutics Inc., Lexington, MA 04241-3108, USA
6 The Feinstein Institute for Medical Research, North Shore--LIJ Health System, Manhasset, NY 11030, USA; Department of Medicine, North Shore University Hospital and NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
7 Department of Internal Medicine, Rheinische Friedrich-Wilhelm Universitaet, Sigmund Freud Strasse 25, Bonn, Germany
8 The Feinstein Institute for Medical Research, North Shore--LIJ Health System, Manhasset, NY 11030, USA; Department of Medicine, North Shore University Hospital and NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA; Present address: Moorse UCSD Cancer Center, 3855 Health Science Drive, La Jolla, CA 92093-0820, USA
Davorka Messmer, E-mail: dmessmer{at}ucsd.edu
Abstract 
, IL-2, IL-5, IL-8, IL-12 and tumor necrosis factor (TNF)-
, but not IL-6 and IL-10. Furthermore, four peptides whose sequences correspond to different regions of HMGB1 induced production of IL-1, IL-2 and IL-12 (p70), but not IL-10 and IL-6 in mouse BM-DCs. Interestingly, these peptides differed in their capacity to induce TNF-, IL-5, IL-18 and IL-8. B box domain as well as peptide-activated DCs acted as potent stimulators of allogeneic T cells in a mixed leukocyte reaction. DCs exposed to HMGB1 peptides induced proliferation of ovalbumin-specific syngeneic T cells. These DC-activating peptides could serve as an adjuvant in immunotherapeutic or vaccine context and the selective activity of these different peptides suggests a means to customize the functional properties of DCs.
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  J. Han, J. Zhong, W. Wei, Y. Wang, Y. Huang, P. Yang, S. Purohit, Z. Dong, M.-H. Wang, J.-X. She, et al. Extracellular High-Mobility Group Box 1 Acts as an Innate Immune Mediator to Enhance Autoimmune Progression and Diabetes Onset in NOD Mice Diabetes, August 1, 2008; 57(8): 2118 - 2127. [Abstract] [Full Text] [PDF]
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