Chemokines (CCL3, CCL4, and CCL5) Inhibit ATP-Induced Release of IL-1β by Monocytic Cells

Figure 7

Schematic presentation of the proposed mechanism. The binding of extracellular ATP to P2X7 receptor on LPS-primed human monocytic U937 cells results in formation of a multiprotein complex called inflammasome that, in turn, activates caspase-1. Caspase-1 catalyzes the proteolytic maturation of pro-IL-1β and enables the release of mature, bioactive IL-1β. We propose that when U937 cells are stimulated with ATP and chemokine CCL3 concomitantly, chemokine receptor CCR1 activates the calcium-independent phospholipase A2 (iPLA2) and the secretion of a small agonist of nicotinic acetylcholine receptors (nAChR). Stimulation of nAChR containing subunits α7 and α9 inhibits P2X7 receptor function and, hence, maturation and secretion of IL-1β. It is still unclear if nAChR subunits of monocytic cells actually form conventional pentamers as shown in the schematic drawing.