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Anti-inflammatory functions of the "apoptotic" caspases

David Wallach1, Tae-Bong Kang, Akhil Rajput

  • 1Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel. d.wallach@weizmann.ac.il

Annals of the New York Academy of Sciences
|October 21, 2010
PubMed

Insights

Caspases regulate inflammation through opposing actions. Apoptotic caspases, like caspase-8, prevent inflammation by controlling cell death and restricting foreign RNA activation of the RIG-I complex, thus preventing chronic skin inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Caspases play dual roles in inflammation: inflammatory caspases promote it, while apoptotic caspases inhibit it.
  • Apoptotic caspases prevent inflammation by controlling cell death, alarmin release, and anti-inflammatory mediator generation.
  • Caspase-8, an apoptotic caspase, also inhibits inflammation by regulating the RIG-I complex.

Purpose of the Study:

  • To investigate the additional anti-inflammatory mechanisms of caspase-8.
  • To understand the role of caspase-8 in regulating the RIG-I complex and preventing chronic skin inflammation.

Main Methods:

  • Studying the function of caspase-8 in apoptotic cell-death induction.
  • Analyzing caspase-8-deficient mice models with chronic skin inflammation.
  • Investigating the activation of the RIG-I complex in keratinocytes.

Main Results:

  • Caspase-8 restricts the activation of the RIG-I complex by foreign ribonucleic acid.
  • Mice lacking caspase-8 in their epidermis exhibit chronic skin inflammation.
  • This inflammation is linked to constitutive RIG-I complex activation in keratinocytes due to released nucleic acids.

Conclusions:

  • Caspase-8 possesses additional anti-inflammatory functions beyond its role in apoptosis.
  • Caspase-8 deficiency leads to uncontrolled RIG-I activation and chronic skin inflammation.
  • The findings highlight caspase-8's critical role in preventing inflammatory responses mediated by nucleic acid sensing.

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