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Brain Behav Immun. 2008 Feb;22(2):234-44. Epub 2007 Oct 1.

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

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  • 1PsyNuGen, INRA, UMR1286, CNRS, UMR5226, Université Victor Ségalen Bordeaux 2, 146 Rue Léo Saignat, 33077 Bordeaux, France.

Abstract

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.

PMID:
17905568
PMCID:
PMC2908086
DOI:
10.1016/j.bbi.2007.08.007
[PubMed - indexed for MEDLINE]
Free PMC Article
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