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Blood, 15 January 2006, Vol. 107, No. 2, pp. 827-834. Prepublished online as a Blood First Edition Paper on September 20, 2005; DOI 10.1182/blood-2005-05-1820. This Article Full Text (PDF) All Versions of this Article: 2005-05-1820v1 107/2/827    most recent Alert me when this article is cited Alert me if a correction is posted 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 Vodanovic-Jankovic, S. Articles by Drobyski, W. R Search for Related Content PubMed PubMed Citation Articles by Vodanovic-Jankovic, S. Articles by Drobyski, W. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 5, 2005 Accepted September 4, 2005 NF-B as a target for the prevention of graft versus host disease: comparative efficacy of bortezomib and PS-1145 Sanja Vodanovic-Jankovic, Parameswaran Hari, Paulette Jacobs, Richard Komorowski, and William R Drobyski* Bone Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, WI, USA; Departments of Medicine and Pathology, Medical College of Wisconsin, Milwaukee, WI, USA * Corresponding author; email: bill{at}bmt.mcw.edu. NF-B is a transcription factor that controls expression of a number of genes that are important for mediating immune and inflammatory responses. In this study, we examined whether bortezomib and PS-1145, which both inhibit NF-B, could protect mice from lethal graft versus host disease (GVHD) which is characterized by immune activation and proinflammatory cytokine production. When administered within the first two days post-transplantation, both bortezomib and PS-1145 protected mice from fatal GVHD, did not compromise donor engraftment, and effected a marked reduction in the levels of serum cytokines that are normally increased during GVHD. Extending the course of bortezomib administration or delaying the initiation of this agent for as little as three days post-BMT, however, significantly exacerbated GVHD-dependent mortality due to severe pathological damage in the colon. In contrast, prolonged administration of PS-1145, which in contrast to bortezomib is a selective inhibitor of NF-B, caused no early toxicity and resulted in more complete protection than observed with an abbreviated PS-1145 treatment schedule. These results confirm a critical role for NF-B in the pathophysiology of GVHD and indicate that targeted inhibition of NF-B may have a superior therapeutic index and constitute a viable therapeutic approach to reduce GVHD severity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Koreth, K. E. Stevenson, H. T. Kim, M. Garcia, V. T. Ho, P. Armand, C. Cutler, J. Ritz, J. H. Antin, R. J. Soiffer, et al. Bortezomib, tacrolimus, and methotrexate for prophylaxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors Blood, October 29, 2009; 114(18): 3956 - 3959. [Abstract] [Full Text] [PDF] K. Sun, M. Li, T. J. Sayers, L. A. Welniak, and W. J. Murphy Differential effects of donor T-cell cytokines on outcome with continuous bortezomib administration after allogeneic bone marrow transplantation Blood, August 15, 2008; 112(4): 1522 - 1529. [Abstract] [Full Text] [PDF] Y. A. Taher, B. C. A. M. van Esch, G. A. Hofman, P. A. J. Henricks, and A. J. M. van Oosterhout 1{alpha},25-Dihydroxyvitamin D3 Potentiates the Beneficial Effects of Allergen Immunotherapy in a Mouse Model of Allergic Asthma: Role for IL-10 and TGF-{beta} J. Immunol., April 15, 2008; 180(8): 5211 - 5221. [Abstract] [Full Text] [PDF] S. P. Chapoval, A. Al-Garawi, J. M. Lora, I. Strickland, B. Ma, P. J. Lee, R. J. Homer, S. Ghosh, A. J. Coyle, and J. A. Elias Inhibition of NF-{kappa}B Activation Reduces the Tissue Effects of Transgenic IL-13 J. Immunol., November 15, 2007; 179(10): 7030 - 7041. [Abstract] [Full Text] [PDF] K. P. A. MacDonald, R. D. Kuns, V. Rowe, E. S. Morris, T. Banovic, H. Bofinger, B. O'Sullivan, K. A. Markey, A. L. Don, R. Thomas, et al. Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD Blood, June 1, 2007; 109(11): 5049 - 5057. [Abstract] [Full Text] [PDF] A. Nencioni, K. Schwarzenberg, K. M. Brauer, S. M. Schmidt, A. Ballestrero, F. Grunebach, and P. Brossart Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation Blood, July 15, 2006; 108(2): 551 - 558. [Abstract] [Full Text] [PDF]

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