Engagement of the LPS receptor enhances activation of various adaptor proteins such as MyD88, IRAK-4, and IRAK-1 to the CD14-TLR4 complex (8). Subsequently, IRAK-1 becomes phosphorylated and then interacts with TRAF6 leading to activation of IKK kinase (23). Because we observed that acute and chronic alcohol exposure does not affect CD14 or TLR4 expression, we sought to determine whether any intracellular membrane-proximal signaling molecules were affected during alcohol exposure of human monocytes. In contrast to decreased LPS-induced IRAK-1 kinase activity by acute alcohol observed in our previous study (17), in this study we found that chronic alcohol augmented LPS-induced IRAK-1 kinase activity (Fig. 2B), indicating that acute and chronic alcohol exposure differently modulates IRAK-1 kinase activity.
