1. Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
- Author
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Florencia C. Mansilla, María C. Miraglia, Silvina S. Maidana, Randazzo Cecilia, and Alejandra V. Capozzo
- Subjects
M2b macrophages ,Muramyl-dipeptide ,NOD2 ,LPS resistance ,PARP-1 ,Biology (General) ,QH301-705.5 ,Medicine - Abstract
Innate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized in-vitro the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation. RAW264.7 cells were trained with MDP (1 μg/ml, 48 h) and challenged with LPS (5 μg/ml, 24 h). Trained cells formed multinucleated giant cells with increased phagocytosis rates compared to untrained/challenged cells. They showed a reduced mitochondrial activity and a switch to aerobic glycolysis. TNF-α, ROS and NO were upregulated in both trained and untrained cultures (MDP+, MDP- cells, p > 0.05); while IL-10, IL-6 IL-12 and MHCII were upregulated only in trained cells after LPS challenge (MDP + LPS+, p
- Published
- 2024
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