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Going up in flames: necrotic cell injury and inflammatory diseases

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Abstract

Recent evidence indicates that cell death can be induced through multiple mechanisms. Strikingly, the same death signal can often induce apoptotic as well as non-apoptotic cell death. For instance, inhibition of caspases often converts an apoptotic stimulus to one that causes necrosis. Because a dedicated molecular circuitry distinct from that controlling apoptosis is required for necrotic cell injury, terms such as “programmed necrosis” or “necroptosis” have been used to distinguish stimulus-dependent necrosis from those induced by non-specific traumas (e.g., heat shock) or secondary necrosis induced as a consequence of apoptosis. In several experimental models, programmed necrosis/necroptosis has been shown to be a crucial control point for pathogen- or injury-induced inflammation. In this review, we will discuss the molecular mechanisms that regulate programmed necrosis/necroptosis and its biological significance in pathogen infections, drug-induced cell injury, and trauma-induced tissue damage.

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Acknowledgments

This work is supported by NIH grants AI088502 and AI083497 (to F.K.C.). F.K.C. is a member of the UMass DERC (DK32520). We thank J. Upton, W. Kaiser and E. Mocarski for sharing their results ahead of print publication.

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Authors and Affiliations

  1. Department of Pathology, Immunology and Virology Program Diabetes and Endocrinology Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA

    Sreerupa Challa & Francis Ka-Ming Chan

  2. Department of Pathology, University of Massachusetts Medical School, Room S2-125, Worcester, MA, 01655, USA

    Francis Ka-Ming Chan

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  1. Sreerupa Challa
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  2. Francis Ka-Ming Chan
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Correspondence to Francis Ka-Ming Chan.

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Challa, S., Chan, F.KM. Going up in flames: necrotic cell injury and inflammatory diseases. Cell. Mol. Life Sci. 67, 3241–3253 (2010). https://doi.org/10.1007/s00018-010-0413-8

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  • DOI: https://doi.org/10.1007/s00018-010-0413-8

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