Signals emanating from the IRAK-1 activation lead to activation of the inhibitor of κB kinase (IKK) complex that mediates phosphorylation of IκBα and activation of NFκB (23). Because we observed that acute and chronic alcohol regulates IRAK-1 activation inversely, we next evaluated whether the acute and chronic alcohol exposure of human monocytes regulates down-stream IKK kinase activity. Fig. 4 shows that while acute alcohol exposure decreased IKK-β kinase activity, chronic alcohol increased IKK-β kinase activity. These results are in agreement with decreased activation of proximal IRAK-1 in acute alcohol treated cells and enhanced IRAK-1 activation after chronic alcohol exposure in monocytes.
