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Critical Reviews™ in Immunology

Impact factor: 3.889

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v29.i4.40
pages 335-345

Modulation of the ATP-lnduced Release and Processing of IL-1β in Microglial Cells

Takato Takenouchi
Transgenic Animal Research Center, National Institute of Agrobiological Sciences; and Laboratory for Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, Japan
Shuei Sugama
Laboratory for Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience; and Department of Physiology, Nippon Medical School, Japan
Yoshifumi Iwamaru
Prion Disease Research Center, National Institute of Animal Health, Kannondai 3-1-5, Tsukuba, Ibaraki 305-8602, Japan
Makoto Hashimoto
Laboratory for Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan
Hiroshi Kitani
Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Japan

ABSTRACT

IL-1β 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-1β from microglia may provide therapeutic clues for neuroinflammatory/neurodegenerative diseases. IL-1β lacks a secretory signal sequence, and thus is not transported through the classical cndoplasmic reticulum/ Golgi-mediated pathway. Although the mechanisms for the release of mature IL-1β still remain controversial, emerging evidence suggests the pivotal roles of the P2X7 receptor (P2X7R), 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 P2X7R-dependent maturation and the release of IL-1β from microglial cells, focusing on the novel roles of lysophospholipids in this process.