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Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Anthrax lethal toxin rapidly activates caspase-1/ICE and induces extracellular release of interleukin (IL)-1beta and

Ruth Cordoba-Rodriguez1, Hui Fang, Carla S R Lankford

  • 1Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. frucht@cber.fda.gov

The Journal of Biological Chemistry
|March 11, 2004
PubMed

Insights

Anthrax lethal toxin (LT) triggers the release of inflammatory cytokines IL-1beta and IL-18 from macrophages. This process is dependent on IL-1beta-converting enzyme (ICE), offering new targets for anthrax therapies.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Anthrax lethal toxin (LT) is a key virulence factor of Bacillus anthracis.
  • LT inactivates MAPKKs, crucial for macrophage survival signals.
  • The effect of LT on proinflammatory cytokine production by macrophages remains debated.

Purpose of the Study:

  • To investigate whether anthrax LT induces the release of proinflammatory cytokines from macrophages.
  • To elucidate the mechanisms underlying LT-induced cytokine release.

Main Methods:

  • Treatment of murine macrophage cell lines (RAW264.7 and J774A.1) with anthrax LT.
  • Analysis of interleukin (IL)-1beta and IL-18 processing and release.
  • Assessment of IL-1beta-converting enzyme (ICE) activation and inhibition.

Main Results:

  • Anthrax LT treatment specifically induced extracellular release of IL-1beta and IL-18.
  • LT enhanced the processing and activation of IL-1beta.
  • Increased IL-1beta processing correlated with heightened ICE activation.
  • The release of IL-1beta and IL-18 was dependent on ICE activity.

Conclusions:

  • ICE, IL-1beta, and IL-18 are downstream effectors of anthrax LT in macrophages.
  • These findings establish a mechanistic link between LT and specific cytokine release.
  • The study provides a basis for developing novel bioassays for anthrax LT and potential therapeutic targets.

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