Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues

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

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    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.

    langue originaleAnglais
    Numéro d'article4151
    journalInternational Journal of Molecular Sciences
    Volume24
    Numéro de publication4
    Les DOIs
    étatPublié - 1 févr. 2023

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