Ethanol selectively modulates inflammatory activation signaling of brain microglia

Heasuk Lee, Jaeyoon Jeong, Eunyung Son, Ahmed Mosa, Gyeong Jae Cho, Wan Sung Choi, Jeoung Hee Ha, In Kyeom Kim, Maan Gee Lee, Choong Young Kim, Kyoungho Suk

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

In spite of well-known deleterious effects of alcohol on the nervous system in general, its specific effect on the brain immune system remains poorly understood. In order to better understand the effect of alcohol consumption on the innate immunity and inflammatory responses in the central nervous system (CNS), we sought to determine how ethanol influences inflammatory activation of microglia that function as the resident immune defense system of the brain. After treatment of BV-2 mouse microglial cells or rat primary microglia cultures with various stimuli, nitric oxide (NO) production was measured as an indicator of microglial activation. Pretreatment of the cells with ethanol (10-100 mM) for 1 h resulted in a significant decrease in lipopolysaccharide (LPS)-induced, but not interferon-gamma (IFNγ)-induced, NO production, indicating that ethanol specifically inhibits LPS-induced inflammatory activation of microglia. This was further supported by the ethanol inhibition of LPS-induced IL-1β expression. In addition, ethanol pretreatment selectively regulated LPS-induced NF-κB signaling pathway without affecting IFNγ-induced signal transducer and activator of transcription 1 (STAT1) phosphorylation, interferon regulatory factor-1 (IRF-1) induction or IFNγ-inducible IP-10 expression. The modulation of LPS-induced NF-κB by ethanol was due to the inhibition of coactivator p300. Altogether, these results suggest that acute ethanol exposure may selectively modulate signal transduction pathways associated with inflammatory activation of microglia, which may lead to derangement of CNS immune and inflammatory responses.

Original languageEnglish
Pages (from-to)88-95
Number of pages8
JournalJournal of Neuroimmunology
Volume156
Issue number1-2
DOIs
StatePublished - Nov 2004

Keywords

  • Cellular activation
  • Ethanol
  • Inflammation
  • Microglia
  • Signal transduction

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