Inhibition of lipopolysaccharide-mediated NF kappa B activation by ethanolin human monocytes

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.