{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:18:35Z","timestamp":1765610315943,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,19]],"date-time":"2023-02-19T00:00:00Z","timestamp":1676764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commissariat G\u00e9n\u00e9ral \u00e0 l\u2019Investissement","award":["BOF09\/01M00709","BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF09\/01M00709","BOF16\/MET_V\/007"]}]},{"name":"Agence Nationale de la Recherche (LabEx LipSTIC, IHU-B Molecular Medicine in Oncology)","award":["BOF09\/01M00709","BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF09\/01M00709","BOF16\/MET_V\/007"]}]},{"name":"Ligue Nationale Contre le Cancer (\u00e9quipe labelis\u00e9e)","award":["BOF09\/01M00709","BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF09\/01M00709","BOF16\/MET_V\/007"]}]},{"name":"Institut National du Cancer (SIRIC SOCRATE)","award":["BOF09\/01M00709","BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF09\/01M00709","BOF16\/MET_V\/007"]}]},{"name":"Methusalem","award":["BOF09\/01M00709","BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF09\/01M00709","BOF16\/MET_V\/007"]}]},{"name":"Methusalem","award":["BOF09\/01M00709","BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF09\/01M00709","BOF16\/MET_V\/007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24044151","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T04:28:57Z","timestamp":1676867337000},"page":"4151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3867-4644","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Solier","sequence":"first","affiliation":[{"name":"INSERM U1170, Gustave Roussy, 94805 Villejuif, France"},{"name":"Faculty of Medicine, Universit\u00e9 Paris-Sud, 94270 Le Kremlin-Bic\u00eatre, 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