LPS-induced IκBα degradation results in NFκB translocation, DNA binding, and transactivation of target genes such as TNF-α (8). When acute alcohol was combined with LPS, LPS-induced NFκB binding activity was significantly decreased in monocytes exposed to alcohol for 1 h (Fig. 7A). However, chronic alcohol exposure of monocytes (4 –7 days) resulted in a significant increase in LPS-induced NFκB activation (Fig. 6A). These results indicate that the opposite effects of acute and chronic alcohol on IRAK-1 and IKK kinase activation extend to differences in NFκB DNA binding activity in human monocytes.
