Fig. 2.

Hypothetical role for the P2X₇ receptor in inflammatory glomerular disease. Following initial injury to the kidney, ATP released from damaged cells, probably together with endogenous Toll-like receptor 4 (TLR4) ligands such as high mobility group box 1 (HMGB1) and lipopolysaccharide (LPS), stimulates the NALP3 inflammasome. Inflammasome activation leads to the maturation of caspase 1, which in turn promotes cleavage, maturation and release of IL-1β and IL-18 from resident macrophages. Released cytokines promote leukocyte influx and stimulate upregulation of P2X₇ on intrinsic renal cells. Prolonged P2X₇ stimulation results in cell death with release of intracellular pro-inflammatory mediators such as ATP, IL-1α and HMGB1, resulting in further rounds of P2X₇ stimulation