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-1 beta and TNF-alpha in mouse brain tissue and isolated microglial cells by activating NF-kappa B. Alcohol activation of NF-kappa B allows for nuclear translocation of the NF-kappa B subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-kappa B pathway by abolishing IKK-beta and IKK-epsilon activity. (C) 2014 Elsevier Inc. All rights reserved.