Amplification and propagation of interleukin-1ß signaling by murine brain endothelial and glial cells.
J Neuroinflammation
; 14(1): 133, 2017 07 01.
Article
em En
| MEDLINE
| ID: mdl-28668091
ABSTRACT
BACKGROUND:
During acute infections and chronic illnesses, the pro-inflammatory cytokine interleukin-1ß (IL-1ß) acts within the brain to elicit metabolic derangements and sickness behaviors. It is unknown which cells in the brain are the proximal targets for IL-1ß with respect to the generation of these illness responses. We performed a series of in vitro experiments to (1) investigate which brain cell populations exhibit inflammatory responses to IL-1ß and (2) examine the interactions between different IL-1ß-responsive cell types in various co-culture combinations.METHODS:
We treated primary cultures of murine brain microvessel endothelial cells (BMEC), astrocytes, and microglia with PBS or IL-1ß, and then performed qPCR to measure inflammatory gene expression or immunocytochemistry to evaluate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. To evaluate whether astrocytes and/or BMEC propagate inflammatory signals to microglia, we exposed microglia to astrocyte-conditioned media and co-cultured endothelial cells and glia in transwells. Treatment groups were compared by Student's t tests or by ANOVA followed by Bonferroni-corrected t tests.RESULTS:
IL-1ß increased inflammatory gene expression and NF-κB activation in primary murine-mixed glia, enriched astrocyte, and BMEC cultures. Although IL-1ß elicited minimal changes in inflammatory gene expression and did not induce the nuclear translocation of NF-κB in isolated microglia, these cells were more robustly activated by IL-1ß when co-cultured with astrocytes and/or BMEC. We observed a polarized endothelial response to IL-1ß, because the application of IL-1ß to the abluminal endothelial surface produced a more complex microglial inflammatory response than that which occurred following luminal IL-1ß exposure.CONCLUSIONS:
Inflammatory signals are detected, amplified, and propagated through the CNS via a sequential and reverberating signaling cascade involving communication between brain endothelial cells and glia. We propose that the brain's innate immune response differs depending upon which side of the blood-brain barrier the inflammatory stimulus arises, thus allowing the brain to respond differently to central vs. peripheral inflammatory insults.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Transdução de Sinais
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Neuroglia
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Células Endoteliais
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Interleucina-1beta
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Neuroinflammation
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos