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Related Concept Videos

Caspases01:24

Caspases

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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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Reprogramming monocyte-derived macrophages through caspase inhibition.

Paul Chaintreuil1, Lucie Laplane2,3, Florian Esnault1

  • 1INSERM U1065, C3M, Université Côte d'Azur, Nice, France.

Oncoimmunology
|March 7, 2022
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Summary

Caspase activation is crucial for macrophage polarization. A pan-caspase inhibitor, Emricasan, prevents this polarization and reprograms macrophages, suggesting its potential for treating diseases involving monocyte-derived macrophages.

Keywords:
CSF-1Primary monocytecaspasesdifferentiationemricasanmonocyte-derived macrophagespolarization

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Macrophages are key innate immune cells involved in diverse physiological and pathological processes.
  • Caspases, known for apoptosis, also have non-apoptotic functions, particularly in monocyte differentiation.
  • Previous work highlighted caspase roles in CSF-1-induced differentiation.

Purpose of the Study:

  • To investigate the role of caspases in IL-4-induced macrophage polarization.
  • To evaluate the effect of a pan-caspase inhibitor, Emricasan, on monocyte-derived macrophage polarization and reprogramming.

Main Methods:

  • Analysis of non-canonical caspase cleavage during IL-4-induced macrophage polarization.
  • Treatment of monocyte-derived macrophages with Emricasan ex vivo.
  • RNA sequencing to assess cellular reprogramming upon caspase inhibition.

Main Results:

  • Non-canonical caspase activation occurs during IL-4-induced macrophage polarization.
  • Emricasan inhibited the generation and anti-inflammatory polarization of monocyte-derived macrophages.
  • Caspase inhibition led to significant reprogramming of monocyte-derived cells, as shown by RNA sequencing.

Conclusions:

  • Caspase activity is essential for the polarization of monocyte-derived macrophages.
  • Emricasan effectively blocks macrophage polarization and induces reprogramming.
  • Emricasan represents a potential therapeutic strategy for diseases driven by monocyte-derived macrophages.