Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by β-amyloid

Abstract : Brain inflammation is characterized by a reactive gliosis involving the activation of astrocytes and microglia. This process, common to many brain injuries and diseases, underlies important phenotypic changes in these two glial cell types. One characteristic feature of astrocytes is their high level of intercellular communication mediated by gap junctions. Previously, we have reported that astrocyte gap junctional communication (AGJC) and the expression of connexin 43 (Cx43), the main constitutive protein of gap junctions, are inhibited in microglia (MG)-astrocyte cocultures. Here, we report that bacterial lipopolysaccharide activation of microglia increases their inhibitory effect on Cx43 expression and AGJC. This inhibition is mimicked by treating astrocyte cultures with conditioned medium harvested from activated microglia. Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were identified as being the main factors responsible for this conditioned medium-mediated activity. Interestingly, an inflammatory response characterized by MG activation and reactive astrocytes occurs in Alzheimer's disease, at sites of beta-amyloid (Abeta) deposits. We found that this peptide potentiates the inhibitory effect of a conditioned medium diluted at a concentration that is not effective per se. This potentiation is prevented by treating astrocytes with specific blockers of IL-1beta and TNF-alpha activities. Thus, the suppression of communication between astrocytes, induced by activated MG could contribute to the proposed role of reactive gliosis in this neurodegenerative disease.
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https://hal.archives-ouvertes.fr/hal-02149161
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Submitted on : Thursday, June 6, 2019 - 10:49:05 AM
Last modification on : Friday, June 7, 2019 - 1:15:18 AM

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William Même, Charles-Félix Calvo, Nicolas Froger, Pascal Ezan, Edwige Amigou, et al.. Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by β-amyloid. FASEB Journal, Federation of American Society of Experimental Biology, 2006, 20 (3), pp.494-496. ⟨10.1096/fj.05-4297fje⟩. ⟨hal-02149161⟩

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