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

Rozenn Mingam, Véronique De Smedt, Thierry Amédée, Rose-Marie Bluthé, Keith W. Kelley, Robert Dantzer, Sophie Layé
Brain, Behavior, and Immunity. 2008-02-01; 22(2): 234-244
DOI: 10.1016/j.bbi.2007.08.007

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1. 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.

Mingam R(1), De Smedt V, Amédée T, Bluthé RM, Kelley KW, Dantzer R, Layé S.

Author information:
(1)PsyNuGen, INRA, UMR1286, CNRS, UMR5226, Université Victor Ségalen Bordeaux 2,
146 Rue Léo Saignat, 33077 Bordeaux, France.

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.

DOI: 10.1016/j.bbi.2007.08.007
PMCID: PMC2908086
PMID: 17905568 [Indexed for MEDLINE]

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