Activation of JNK has been shown to be important in many models of hepatotoxicity [29–32], including CYP2E1 potentiation of LPS or TNF liver injury [33,34]. There are few studies evaluating the role of JNK, if any, in ethanol-induced hepatotoxicity and steatosis. Fig. 5 shows that JNK2 (54KDa) was elevated 50% (0.6 to 0.9 pJNK2/JNK2 ratio) in wild type mice chronically fed ethanol as compared to pair-fed controls. This modest activation of JNK2 did not occur in the CYP2E1 knockout mice fed ethanol. However activation of JNK2 was restored, and even magnified (3-fold) in the CYP2E1 knockin mice fed ethanol (Fig. 5). JNK1 (46 KDa), which was not activated in the ethanol-fed wild type or CYP2E1 knockout mice, was activated 5-fold in the ethanol fed CYP2E1 knockin mice (Fig. 5). We did not observe any activation of p38MAPK by ethanol in any group (data not shown).
