In vitro and in vivo evidence for a role of the P2X7 receptor in the release of IL-1 beta in the murine brain

Brain Behav Immun. 2008 Feb;22(2):234-44. doi: 10.1016/j.bbi.2007.08.007. Epub 2007 Oct 1.


The P2X(7) receptor (P2X(7)R) is a purinoceptor expressed predominantly by cells of immune origin, including microglial cells. P2X(7)R has a role in the release of biologically active proinflammatory cytokines such as IL-1 beta, IL-6 and TNFalpha. Here we demonstrate that when incubated with lipopolysaccharide (LPS), glial cells cultured from brain of P2X(7)R(-/-) mice produce less IL-1 beta compared to glial cells from brains of wild-type mice. This is not the case for TNFalpha and IL-6. Our results indicate a selective effect of the P2X7R gene deletion on release of IL-1 beta release but not of IL-6 and TNFalpha. In addition, we confirm that only microglial cells produce IL-1beta, and this release is dependent on P2X(7)R and ABC1 transporter. Because IL-1 beta is a key regulator of the brain cytokine network and P2X(7)R is an absolute requirement for IL-1 beta release, we further investigated whether response of brain cytokines to LPS in vivo was altered in P2X(7)R(-/-) mice compared to wild-type mice. IL-1 beta and TNFalpha mRNAs were less elevated in the brain of P2X(7)R(-/-) than in the brain of wild-type mice in response to systemic LPS. These results show that P2X7R plays a key role in the brain cytokine response to immune stimuli, which certainly applies also to cytokine-dependent alterations in brain functions including sickness behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Hypothalamus / cytology
  • Hypothalamus / immunology*
  • Hypothalamus / metabolism
  • Interleukin-1beta / metabolism*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / immunology*
  • Neuroimmunomodulation / immunology*
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / immunology*
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2X7
  • Tumor Necrosis Factor-alpha / metabolism


  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • P2rx7 protein, mouse
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Tumor Necrosis Factor-alpha