Modulation of the ATP-Induced Release and Processing of IL-1 beta in Microglial Cells

IL-1 beta is one of the most potent proinflammatory cytokines. It is primarily released from activated microglia in the brain, and is also implicated in the induction and progression of pathogenesis in various neurodegenerative disorders. Therefore, to clarify the regulatory or modulatory mechanisms for maturation and release of IL-1 beta from microglia may provide therapeutic clues for neuroinflammatory/neurodegenerative diseases. IL-1 beta lacks a secretory signal sequence, and thus is not transported through the classical endoplasmic reticulum/Golgi-mediated pathway. Although the mechanisms for the release of mature IL-1 beta still remain controversial, emerging evidence suggests the pivotal roles of the P2X(7) receptor (P2X(7)R), one of the ionotropic P2X receptors for extracellular ATP, in the release of this cytokine. Here, we review the current studies regarding the modulatory mechanisms of P2X(7)R-dependent maturation and the release of IL-1 beta from microglial cells, focusing on the novel roles of lysophospholipids in this process.