Stress and AODs, as well as sensory and hormonal signals, activate a regulatory protein (i.e., transcription factor3) called nuclear factor κ–light-chain enhancer of activated B cells (NF-κB) that is produced in large amounts (i.e., is highly expressed) in monocytes and microglia. Although NF-κB is found in most cells, it is the key transcription factor involved in the induction of innate immune genes in microglia and other monocyte-like cells. A wide range of stimuli, such as stress, cytokines, oxidative free radicals, ultraviolet irradiation, bacterial or viral molecules, and many other signaling molecules, increase binding of NF-κB to specific sequences of the DNA. This binding increases the transcription of many genes, particularly those encoding signaling molecules (e.g., chemokines and cytokines) and enzymes (e.g., oxidases and proteases) (figure 3). Studies found that ethanol can increase the binding of NF-κB to its corresponding DNA sequences both in the brains of living organisms (Crews et al. 2006) and in cultured brain slices obtained from a brain area called the hippocampal–entorhinal cortex (HEC) (Zou and Crews 2006). These and other studies also have indicated that ethanol
