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Journal of Neuroinflammation

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Open Access 01-12-2019 | Neuropathic Pain | Research

BET protein inhibition regulates cytokine production and promotes neuroprotection after spinal cord injury

Authors: Judith Sánchez-Ventura, Jesús Amo-Aparicio, Xavier Navarro, Clara Penas

Published in: Journal of Neuroinflammation | Issue 1/2019

Abstract

Background

Spinal cord injury (SCI) usually causes a devastating lifelong disability for patients. After a traumatic lesion, disruption of the blood-spinal cord barrier induces the infiltration of macrophages into the lesion site and the activation of resident glial cells, which release cytokines and chemokines. These events result in a persistent inflammation, which has both detrimental and beneficial effects, but eventually limits functional recovery and contributes to the appearance of neuropathic pain. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that regulate the expression of inflammatory genes by interacting with acetylated lysine residues. While BET inhibitors are a promising therapeutic strategy for cancer, little is known about their implication after SCI. Thus, the current study was aimed to investigate the anti-inflammatory role of BET inhibitors in this pathologic condition.

Methods

We evaluated the effectiveness of the BET inhibitor JQ1 to modify macrophage reactivity in vitro and to modulate inflammation in a SCI mice model. We analyzed the effects of BET inhibition in pro-inflammatory and anti-inflammatory cytokine production in vitro and in vivo. We determined the effectiveness of BET inhibition in tissue sparing, inflammation, neuronal protection, and behavioral outcome after SCI.

Results

We have found that the BET inhibitor JQ1 reduced the levels of pro-inflammatory mediators and increased the expression of anti-inflammatory cytokines. A prolonged treatment with JQ1 also decreased reactivity of microglia/macrophages, enhanced neuroprotection and functional recovery, and acutely reduced neuropathic pain after SCI.

Conclusions

BET protein inhibition is an effective treatment to regulate cytokine production and promote neuroprotection after SCI. These novel results demonstrate for the first time that targeting BET proteins is an encouraging approach for SCI repair and a potential strategy to treat other inflammatory pathologies.

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Title: BET protein inhibition regulates cytokine production and promotes neuroprotection after spinal cord injury
Authors: Judith Sánchez-Ventura
Jesús Amo-Aparicio
Xavier Navarro
Clara Penas
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Neuropathic Pain
Cytokines
Published in: Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-019-1511-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

BET protein inhibition regulates cytokine production and promotes neuroprotection after spinal cord injury

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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