The P2X7 receptor/NLRP3 inflammasome signaling axis in sepsis: molecular mechanisms, organ-specific pathophysiology, and emerging therapeutic strategies - PubMed
14 hours ago
- #Sepsis
- #Inflammasome
- #Therapeutic Strategies
- Sepsis is a leading cause of mortality in intensive care units due to dysregulated host responses to infection.
- The P2X7 receptor (P2X7R) and NLRP3 inflammasome are critical regulators of inflammatory responses in sepsis.
- Extracellular ATP activates P2X7R, leading to potassium efflux and NLRP3 inflammasome assembly.
- The NLRP3 inflammasome mediates caspase-1-dependent maturation of IL-1β and IL-18, and induces pyroptotic cell death via gasdermin D (GSDMD).
- Excessive P2X7R activation during sepsis can cause mitochondrial dysfunction in monocytes, leading to immunoparalysis and increased mortality.
- The review examines the dual roles of P2X7/NLRP3 signaling in hyperinflammation and immunosuppression.
- Organ-specific manifestations of sepsis in the lung, kidney, heart, brain, liver, and intestine are discussed.
- Emerging therapeutic strategies include NLRP3 inhibitors (e.g., MCC950), P2X7R antagonists, IL-1 receptor blockade, GSDMD inhibitors, and natural compounds.
- Understanding the temporal dynamics of P2X7/NLRP3 signaling is crucial for developing targeted sepsis interventions.