Inhibition of lipopolysaccharide-mediated NFκB activation by ethanol in human monocytes

Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Alcohol use is typically associated with impaired immunity and increased host susceptibility to infection, partially due to decreased inflammatory response. Acute ethanol exposure has been shown to down-regulate monocyte production of inflammatory cytokines. Activation of the pluripotent transcription factor NFκB is a pivotal step in the induction of inflammatory cytokines, chemokines and growth factors. Therefore, we hypothesized that alcohol may alter NFκB activation, thus providing a mechanism for the decreased inflammatory cytokine production by monocytes after acute alcohol treatment. We show here for the first time that alcohol inhibits lipopolysaccharide (LPS)-induced NFκB activation in human monocytes by decreasing DNA binding of the p65/p50 heterodimer as seen in electrophoretic mobility shift and supershift assays. We also demonstrate that alcohol prevents LPS-induced nuclear translocation of p65 and to a lesser extent that of the p50 subunits. NFκB activation is regulated via phosphorylation and proteolytic degradation of IκB. Thus, we investigated the effect of acute ethanol treatment on IκB in human monocytes. Alcohol did not prevent LPS-induced IκBα degradation but decreased the levels of phospho-specific IκBα (Ser32). Finally, for the first time we show that de novo protein synthesis is necessary to bring about the ethanol-mediated inhibition of LPS-induced NFκB activation. Consequently, these results suggest that physiologically relevant concentrations of alcohol interfere with NFκB activation and thereby may affect the regulation of NFκB-controlled gene activation.

Original languageEnglish
Pages (from-to)1781-1790
Number of pages10
JournalInternational Immunology
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 24 1999

Keywords

  • Alcohol
  • Inflammatory cytokines
  • Intracellular signaling
  • Macrophages
  • Nuclear regulatory factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Inhibition of lipopolysaccharide-mediated NFκB activation by ethanol in human monocytes'. Together they form a unique fingerprint.

  • Cite this