Alcohol metabolizing enzymes such as CYP2E1 play an important role in oxidative stress related liver injury (29) and is directly involved in production of reactive oxygen species. Human monocyte-derived macrophages induce CYP2E1 in response to alcohol treatment at a level lower than the liver cells but similar to other extrahepatic tissues (30). Reactive oxygen species generation due to CYP2E1 has been shown to directly affect NFκB activation, and this could influence inflammatory cytokine gene expression (31). Because chronic alcohol induces NFκB activation, using 4-methyl pyrazole, a pharmacological inhibitor of CYP2E1 and cyanamide, an aldehyde dehydrogenase inhibitor we determined whether alcohol metabolism was involved in this effect. Fig. 7C shows that chronic alcohol exposure over a period of 7 days moderately induced CYP2E1 in human monocytes. Inhibition of alcohol metabolizing enzymes using 4-methyl pyrazole and cyanamide however, did not affect chronic alcohol-induced NFκB DNA binding activity (Fig. 7D) and LPS-induced TNF-α levels (Fig. 7E), suggesting that although chronic alcohol induces CYP2E1 in human monocytes, the effect of alcohol on NFκB regulation is CYP2E1 independent.
