Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 4, p 4151 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms24044151
Popis: 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.
Databáze: Directory of Open Access Journals
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