NFκB activation is a major regulator of LPS-induced inflammatory cascade signaling. LPS induced IKK kinase activation culminates in rapid degradation of cytoplasmic IκBα (8). LPS stimulation of human monocytes revealed decreased IκBα in the cytoplasmic extracts suggesting that NFκB activation was accompanied by IκBα degradation (Fig. 6). As shown previously by our group (19, 20), our results in this study confirm that IκBα levels remained low in LPS plus acute alcohol exposed monocytes even though IKK kinase activity was reduced in these cells (Fig. 4). Interestingly, chronic alcohol exposure for 4 –7 days followed by LPS stimulation resulted in decreased IκBα levels in the cytoplasm, indicating that IKK kinase activation may induce IκBα degradation in chronic alcohol-exposed monocytes. These results suggest that while acute alcohol-induced IκBα degradation could be independent of IKK kinase, chronic alcohol-induced IκBα degradation is dependent on IKK kinase activity.
