Signaling Through Purinergic Receptor P2Y2Enhances Macrophage IL-1β Production

The release of nucleotides during necrosis or apoptosis has been described to have both proinflammatory and anti-inflammatory effect on the surrounding cells. Here we describe how low concentrations of UTP and ATP applied during macrophage priming enhance IL-1 beta production when subsequently the NLRP3 inflammasome is activated in murine resident peritoneal macrophages. Deficiency or pharmacological inhibition of the purinergic receptor P2Y(2)reverted the increase of IL-1 beta release induced by nucleotides. IL-1 beta increase was found dependent on the expression ofIl1bgene and probably involving JNK activity. On the contrary, nucleotides decreased the production of a different proinflammatory cytokines such as TNF-alpha. These results suggest that nucleotides could shape the response of macrophages to obtain a unique proinflammatory signature that might be relevant in unrevealing specific inflammatory conditions.