| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
E-mail contact: psoares{at}igc.gulbenkian.pt
Heme oxygenase-1 (HO-1), which degrades heme into three products (carbon monoxide, free iron, and biliverdin), plays a protective role in many models of disease via its anti-inflammatory, anti-apoptotic, and anti-proliferative actions. Overexpression of HO-1 has been shown to suppress immune responses and prolong the survival of allografts; however, the underlying mechanism is not clear. We demonstrate two "new" properties of HO-1 that mediate activation induced cell death (AICD) of allo-antigen-responsive murine CD4+ T cells, resulting in immunomodulation. First, it functions in vivo and in vitro to "boost" the proliferative response of CD4+ T cells to allo-antigens in the early phase of allo-antigen-driven immune responses. This "boosting" effect is accompanied with a significant increase of activation markers and IL-2 production. Second, it exerts a pro-apoptotic effect in those activated T cells after the initial burst of proliferation. We further show that the AICD effect is mediated through the Fas/CD95-FasL signal transduction pathway. Correlating with the above-mentioned findings is the observed prolongation of mouse heart graft survival when HO-1 is expressed in vivo in both donor and recipient. In conclusion, induction of HO-1 expression accelerates clonal deletion of peripheral alloreactive CD4+ T cells by promoting AICD, which is presumably a key mechanism for its immunomodulatory effects such as in prolonging the survival of transplanted organs.
Key words: T lymphocytes • apoptosis • cellular activation
This article has been cited by other articles:
|
|
 |
|
  E. Seixas, R. Gozzelino, A. Chora, A. Ferreira, G. Silva, R. Larsen, S. Rebelo, C. Penido, N. R. Smith, A. Coutinho, et al. From the Cover: Heme oxygenase-1 affords protection against noncerebral forms of severe malaria PNAS, September 15, 2009; 106(37): 15837 - 15842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsushima, H. Tanaka, N. Mizumoto, and A. Takashima Identification of crassin acetate as a new immunosuppressant triggering heme oxygenase-1 expression in dendritic cells Blood, July 2, 2009; 114(1): 64 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Seldon, G. Silva, N. Pejanovic, R. Larsen, I. P. Gregoire, J. Filipe, J. Anrather, and M. P. Soares Heme Oxygenase-1 Inhibits the Expression of Adhesion Molecules Associated with Endothelial Cell Activation via Inhibition of NF-{kappa}B RelA Phosphorylation at Serine 276 J. Immunol., December 1, 2007; 179(11): 7840 - 7851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Hu, H.-H. Lin, M.-T. Chiang, P.-F. Chang, and L.-Y. Chau Systemic Expression of Heme Oxygenase-1 Ameliorates Type 1 Diabetes in NOD Mice Diabetes, May 1, 2007; 56(5): 1240 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zelenay, A. Chora, M. P. Soares, and J. Demengeot Heme oxygenase-1 is not required for mouse regulatory T cell development and function Int. Immunol., January 1, 2007; 19(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Was, T. Cichon, R. Smolarczyk, D. Rudnicka, M. Stopa, C. Chevalier, J. J. Leger, B. Lackowska, A. Grochot, K. Bojkowska, et al. Overexpression of Heme Oxygenase-1 in Murine Melanoma: Increased Proliferation and Viability of Tumor Cells, Decreased Survival of Mice Am. J. Pathol., December 1, 2006; 169(6): 2181 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Brusko, C. H. Wasserfall, A. Agarwal, M. H. Kapturczak, and M. A. Atkinson An Integral Role for Heme Oxygenase-1 and Carbon Monoxide in Maintaining Peripheral Tolerance by CD4+CD25+ Regulatory T Cells J. Immunol., May 1, 2005; 174(9): 5181 - 5186. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
