International Immunology, Vol. 11, No. 11, 1781-1790,
November 1999
© 1999 Japanese Society for Immunology
Inhibition of lipopolysaccharide-mediated NF
B activation by ethanol in human monocytes
Division of Rheumatology, Department of Medicine, University of Massachusetts Medical Center,55 Lake Avenue North, Worcester, MA 01655, USA
Correspondence to: G. Szabo
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 NF
B is a pivotal step in the induction of inflammatory cytokines, chemokines and growth factors. Therefore, we hypothesized that alcohol may alter NFB 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 NFB 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. NFB activation is regulated via phosphorylation and proteolytic degradation of IB. Thus, we investigated the effect of acute ethanol treatment on IB in human monocytes. Alcohol did not prevent LPS-induced IB
degradation but decreased the levels of phospho-specific IB (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 NFB activation. Consequently, these results suggest that physiologically relevant concentrations of alcohol interfere with NFB activation and thereby may affect the regulation of NFB-controlled gene activation.
Keywords: alcohol, intracellular signaling, inflammatory cytokines, nuclear regulatory factors, macrophages
Transmitting editor: C. Terhorst
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