P65 | (YS) INVESTIGATING THE EFFECTS OF THE SECRETOME FROM HUMAN AMNIOTIC MESENCHYMAL STROMAL CELLS ON INFLAMMASOME ACTIVATION
Macrophages play a pivotal role in inflammation and, upon exposure to stimuli such as lipopolysaccharides (LPS), they activate the NLRP3 inflammasome – a multiprotein complex of the NOD-like receptor family. This activation drives macrophage polarization toward the pro-inflammatory M1 phenotype thr...
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| Format: | Article |
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| Language: | English |
| Published: |
PAGEPress Publications
2025-08-01
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| Series: | European Journal of Histochemistry |
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| Online Access: | https://www.ejh.it/ejh/article/view/4390 |
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| Summary: | Macrophages play a pivotal role in inflammation and, upon exposure to stimuli such as lipopolysaccharides (LPS), they activate the NLRP3 inflammasome – a multiprotein complex of the NOD-like receptor family. This activation drives macrophage polarization toward the pro-inflammatory M1 phenotype through metabolic reprogramming, reactive oxygen species (ROS) production, and the release of pro-inflammatory cytokines1. The canonical activation pathway of NLRP3 involves the oligomerization of ASC (apoptosis-associated speck-like protein containing a CARD), forming cytosolic aggregates known as ASC specks, and triggers caspase-1 activation and IL-1β maturation2. We previously demonstrated that the secretome from human amniotic mesenchymal stromal cells (hAMSC), also known as conditioned medium (CM-hAMSC), affects macrophage polarization by promoting a shift from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype3. This study investigates whether CM-hAMSC can modulate inflammasome activation in M1 macrophages. Monocytes were differentiated into M1 macrophages using GM-CSF for 5 days and then stimulated with LPS and ATP in presence or absence of CM-hAMSC. After 5 h, inflammasome activation was evaluated as IL-1β release, ASC speck formation and mitochondrial ROS levels through ELISA, fluorescence microscopy and flow cytometry analyses. CM-hAMSC significantly reduced IL-1β secretion and ROS accumulation, with a slight decrease in ASC speck formation. These findings support the anti-inflammatory role of CM-hAMSC and highlights the need for more detailed mechanistic studies.
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| ISSN: | 1121-760X 2038-8306 |