Cellular and Molecular Life Sciences

, Volume 67, Issue 19, pp 3241–3253 | Cite as

Going up in flames: necrotic cell injury and inflammatory diseases

Review

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.

Keywords

RIP1 RIP3 Programmed necrosis Inflammation TNF 

Notes

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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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  1. 1.Department of Pathology, Immunology and Virology Program Diabetes and Endocrinology CenterUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Department of PathologyUniversity of Massachusetts Medical SchoolWorcesterUSA

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