Inflammasome activation by danger signals: extracellular ATP and pH

AbstractExtracellular ATP has been recognized as a danger signal that alerts the innate immune system. High extracellular concentrations of ATP can trigger the maturation and secretion of pro-inflammatory cytokines (e.g., interleukin-1β and interleukin-18) through the inflammasome-dependent activation of caspase-1. The P2X7 receptor, an ATP-gated cation channel, plays a pivotal role in ATP-induced NLRP3 inflammasome assembly. Recently, intriguing evidence has emerged that acidic extracellular pH acts as a danger signal that activates inflammasomes. Extracellular acidification frequently occurs at sites of inflammation, infection, or injury. In addition, large amounts of ATP are readily released into the extracellular space from damaged cells at such sites. Thus, it is assumed that the ATP/P2X7 receptor pathway regulates the inflammatory response under acidic extracellular conditions. Here, we briefly discuss the mutual effects of extracellular ATP and pH on inflammasome activation and consider their roles in the regulation of inflammation.