First published online February 21, 2007
Journal of Cell Science 120, 504e (2007)
© The Company of Biologists Limited
IL-defined processing
The pro-inflammatory cytokine interleukin-1
(IL-1) is implicated in acute and chronic inflammatory diseases. However, despite its biological importance, the mechanisms involved in its processing and trafficking are poorly defined. On p. 772, David Brough and Nancy Rothwell define the cellular mechanisms involved in IL-1 post-translational processing and provide insight into the atypical pathway by which IL-1 is generated. The authors demonstrate that cleavage of the precursor polypeptide Pro-IL-1 by caspase-1 occurs predominantly in the cytosol following activation of the proinflammatory purinergic receptor P2X7 by ATP and suggest a lack of lysosomal involvement. Structural changes to the cell, following caspase-1 activation, promote the cellular release of IL-1, which itself precedes cell death. The authors propose that IL-1 processing occurs in the cytosol by a mechanism that resembles the programmed cell death process, pyroptosis, which requires caspase-1. Understanding mechanisms of bioactive IL-1 generation may help identify new targets for anti-IL-1 therapies and improve our understanding of inflammatory processes during disease.
Related articles in JCS:
- Caspase-1-dependent processing of pro-interleukin-1 is cytosolic and precedes cell death
- David Brough and Nancy J. Rothwell
JCS 2007 120: 772-781.
[Abstract]
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