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Heme Sensitization to TNF-Mediated Programmed Cell Death

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Advances in TNF Family Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 691))

Abstract

The cytotoxic effect of tumor necrosis factor (TNF) is repressed in most cell types through the expression of several immediate–early TNF-responsive cytoprotective genes. To the best of our knowledge, there are no molecules produced under pathophysiologic condition that have been shown to override this cytoprotective effect. Identification of such molecules should contribute to our current understanding of the mechanisms underlying the pathophysiologic effects of TNF. We will argue that free heme acts in such a manner, promoting TNF-driven cytotoxicity, which might be an important component of the pathogenesis of several immune-mediated inflammatory diseases, as illustrated hereby for malaria.

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Abbreviations

Fe:

iron

JNK:

Jun N-terminal kinase

NF-κB:

nuclear factor kappa B

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Acknowledgments

The authors thank Rasmus Larsen for invaluable help in producing the figure of this chapter as well as all members of the inflammation laboratory for critical input in the ideas and data that support the models put forward in this manuscript. This work was supported in part by “Fundação para a Ciência e Tecnologia,” Portugal grants SFRH/BPD/44256/2008 to RG, POCTI/SAU-MNO/56066/2004 and PTDC/SAU-MII/65765/2006 to MPS. Support was also provided by European Community grants, 6th Framework Xenome (LSH-2005-1.2.5-1), and by the Gemi Fund (Linde Healthcare) to MPS.

Author information

Authors and Affiliations

  1. Instituto Gulbenkian de Ciência, Rua da Quinta Grande, Oeiras, Portugal

    Raffaella Gozzelino

  2. Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6,2780-156, Oeiras, Portugal

    Miguel P. Soares

Authors
  1. Raffaella Gozzelino
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  2. Miguel P. Soares
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Corresponding author

Correspondence to Miguel P. Soares .

Editor information

Editors and Affiliations

  1. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    David Wallach

  2. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    Andrew Kovalenko

  3. Kennedy Institute of Rheumatology, Imperial College London, Aspenlea Rd. 1, London, W6 8LH, United Kingdom

    Marc Feldmann

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Gozzelino, R., Soares, M.P. (2011). Heme Sensitization to TNF-Mediated Programmed Cell Death. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_22

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