P. Mandrekar et al., Inhibition of lipopolysaccharide-mediated NF kappa B activation by ethanolin human monocytes, INT IMMUNOL, 11(11), 1999, pp. 1781-1790
Alcohol use is typically associated with impaired immunity and increased ho
st susceptibility to infection, partially due to decreased inflammatory res
ponse. Acute ethanol exposure has been shown to down-regulate monocyte prod
uction of inflammatory cytokines, Activation of the pluripotent transcripti
on factor NF kappa B is a pivotal step in the induction of inflammatory cyt
okines, chemokines and growth factors, Therefore, we hypothesized that alco
hol may alter NF kappa B activation, thus providing a mechanism for the dec
reased inflammatory cytokine production by monocytes after acute alcohol tr
eatment. We show here for the first time that alcohol inhibits lipopolysacc
haride (LPS)-induced NF kappa B 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 p5
0 subunits, NF kappa B activation is regulated via phosphorylation and prot
eolytic degradation of I kappa B. Thus, we investigated the effect of acute
ethanol treatment on I kappa B in human monocytes. Alcohol did not prevent
LPS-induced I kappa B alpha degradation but decreased the levers of phosph
o-specific I kappa B alpha (Ser32), Finally, for the first time we show tha
t de novo protein synthesis is necessary to bring about the ethanol-mediate
d inhibition of LPS-induced NF kappa B activation. Consequently, these resu
lts suggest that physiologically relevant concentrations of alcohol interfe
re with NF kappa B activation and thereby may affect the regulation of NF k
appa B-controlled gene activation.