Abstract
Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.
Keywords:
Alcohol; Brain-inflammation; MicroRNA; NF-κB; miR-339-5p.
Copyright © 2014 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Animals
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Base Sequence
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Brain / drug effects
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Brain / metabolism*
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Brain / pathology
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Encephalitis / chemically induced
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Encephalitis / genetics*
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Encephalitis / metabolism
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Encephalitis / pathology
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Ethanol / pharmacology*
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Gene Expression Regulation
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I-kappa B Kinase / genetics*
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I-kappa B Kinase / metabolism
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Interleukin-1beta / biosynthesis
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Interleukin-1beta / metabolism
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Interleukin-6 / biosynthesis
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Interleukin-6 / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Microglia / drug effects
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Microglia / metabolism
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Microglia / pathology
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Molecular Sequence Data
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Primary Cell Culture
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Protein Transport
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Signal Transduction
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism
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Transcription, Genetic
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Interleukin-1beta
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Interleukin-6
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MicroRNAs
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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Ethanol
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I-kappa B Kinase
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Ikbkb protein, mouse