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Dopamine activates NF-κB and primes the NLRP3 inflammasome in primary human macrophages
Journal article   Open access   Peer reviewed

Dopamine activates NF-κB and primes the NLRP3 inflammasome in primary human macrophages

R.A. Nolan, K.L Reeb, Y. Rong, S. M. Matt, H. S. Johnson, K. Runner and P.J. Gaskill
Brain, behavior, & immunity. Health, v 2, p100030
31 Dec 2019
DOI: https://doi.org/10.1016/j.bbih.2019.100030
PMID: 33665636
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.bbih.2019.100030View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Dopamine drug abuse macrophages neuroinflammation NF-κB NLRP3
Induction of innate immune genes in the brain is thought to be a major factor in the development of addiction to substances of abuse. As the major component of the innate immune system in the brain, aberrant activation of myeloid cells such as macrophages and microglia due to substance use may mediate neuroinflammation and contribute to the development of addiction. All addictive drugs modulate the dopaminergic system and our previous studies have identified dopamine as a pro-inflammatory modulator of macrophage function. However, the mechanism that mediates this effect is currently unknown. Inflammatory activation of macrophages and induction of cytokine production is often mediated by the transcription factor NF-κB, and prior studies have shown that dopamine can modulate NF-κB activity in T-cells and other non-immune cell lines. Here we demonstrated that dopamine can activate NF-κB in primary human macrophages, resulting in the induction of its downstream targets including the NLRP3 inflammasome and the inflammatory cytokine IL-1β. These data also indicate that dopamine primes but does not activate the NLRP3 inflammasome in human macrophages. Activation of NF-κB was required for dopamine-mediated increases in IL-1β, as an inhibitor of NF-κB was able to abrogate the effects of dopamine on production of these cytokines. Connecting an increase in extracellular dopamine to NF-κB activation and inflammation suggests specific intracellular targets that could be used to ameliorate the inflammatory impact of dopamine in neuroinflammatory conditions associated with myeloid cell activation such as addiction.

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45 citations in Scopus

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Web of Science research areas
Immunology
Neurosciences
Psychiatry
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