| First Author | Solier S | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 4 | PubMed ID | 36835566 |
| Mgi Jnum | J:337487 | Mgi Id | MGI:7441197 |
| Doi | 10.3390/ijms24044151 | Citation | Solier S, et al. (2023) Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues. Int J Mol Sci 24(4) |
| abstractText | 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 p47(PHOX) 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. |
