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Article Dans Une Revue International Journal of Molecular Sciences Année : 2023

Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues

Stéphanie Solier
Michele Mondini
Lydia Meziani
  • Fonction : Auteur
Arnaud Jacquel
Catherine Lacout
  • Fonction : Auteur
Tom Vanden Berghe
  • Fonction : Auteur
Yvon Julé
  • Fonction : Auteur
Jean-Claude Martinou
  • Fonction : Auteur
Gérard Pierron
  • Fonction : Auteur
Julie Rivière
Marc Deloger
Corinne Dupuy
  • Fonction : Auteur
Anny Slama-Schwok
Nathalie Droin
Peter Vandenabeele
  • Fonction : Auteur
Patrick Auberger
  • Fonction : Auteur
Eric Deutsch
  • Fonction : Auteur
Jamel El-Benna
Eric Solary

Résumé

Circulating monocytes are recruited in damaged tissues to generate macrophages that modulate disease progression. Colony-stimulating factor-1 (CSF-1) promotes the generation of monocyte-derived macrophages, which involves caspase activation. Here, we demonstrate that activated caspase-3 and caspase-7 are located to the vicinity of the mitochondria in CSF1-treated human monocytes. Active caspase-7 cleaves p47PHOX at aspartate 34, which promotes the formation of the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase complex NOX2 and the production of cytosolic superoxide anions. Monocyte response to CSF-1 is altered in patients with a chronic granulomatous disease, which are constitutively defective in NOX2. Both caspase-7 down-regulation and radical oxygen species scavenging decrease the migration of CSF-1-induced macrophages. Inhibition or deletion of caspases prevents the development of lung fibrosis in mice exposed to bleomycin. Altogether, a non-conventional pathway that involves caspases and activates NOX2 is involved in CSF1-driven monocyte differentiation and could be therapeutically targeted to modulate macrophage polarization in damaged tissues.

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hal-04096797 , version 1 (13-05-2023)

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Stéphanie Solier, Michele Mondini, Lydia Meziani, Arnaud Jacquel, Catherine Lacout, et al.. Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues. International Journal of Molecular Sciences, 2023, 24 (4), pp.4151. ⟨10.3390/ijms24044151⟩. ⟨hal-04096797⟩

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