the CI gene networks assembled for both PFC and liver, the overlap of genes was greater for LPS than for the ethanol treatments (Chronic or DID). This may reflect emerging evidence that ethanol promotes proinflammatory signaling in brain and liver by increasing TLR4 activation and cytokine cascades [12] , [24], [25], [49]–[51]. LPS acts on TLR4 and thus has the potential to share activation of TLR4 function with ethanol, especially in the liver. It is controversial as to whether LPS can cross the blood brain barrier and whether its effects on brain function are likely to be secondary to release of cytokines from liver and other peripheral tissues or a direct effect on brain microglia and endothelia [52], [53]. It is interesting to note that chronic alcohol abuse can compromise the gut and allow leakage of LPS into the systemic circulation and this is important for development of alcoholic liver disease [24]. Although we did not combine LPS and alcohol exposures, our studies showing overlap between the transcriptome modifications produced by the separate treatments supports the proposal that LPS can enhance some of the biological actions of ethanol, and vice versa [49], [50].
