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A perspective on mammalian caspases as positive and negative regulators of inflammation

Seamus J Martin1, Conor M Henry, Sean P Cullen

  • 1Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland. martinsj@tcd.ie

Molecular Cell
|May 29, 2012
PubMed

Insights

Caspases, or cysteine proteases, may not directly cause cell death but instead prevent inflammation from dying cells. This shifts understanding of caspase function in regulating immune responses.

Area of Science:

  • Cellular biology
  • Immunology
  • Biochemistry

Background:

  • Caspase proteases are key to apoptosis, but their inhibition doesn't prevent cell death.
  • Mitochondrial dysfunction and BAX/BAK channel opening often precede caspase activation.
  • Blocking caspases switches cell death from apoptosis to inflammation-provoking necrosis.

Purpose of the Study:

  • To propose an alternative function for caspases in regulating inflammation.
  • To reframe the role of caspases in cell death and immune response.

Main Methods:

  • Review of existing literature on caspases, apoptosis, and necrosis.
  • Analysis of the implications of caspase inactivation on cell death phenotypes.
  • Conceptual synthesis of caspase function in relation to inflammation.

Main Results:

  • Caspase activity is not essential for initiating cell death in most cases.
  • Caspase inactivation converts apoptosis to necrosis, triggering inflammation.
  • Dying cells' proinflammatory properties are actively extinguished by caspases.

Conclusions:

  • Caspases may function primarily to suppress inflammation in dying cells.
  • This perspective unifies caspases as regulators of the immune response.
  • Understanding caspase function is crucial for modulating inflammation in disease.

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