Mechanisms Of Drug-induced Toxicities

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ANNUAL REPORT FOR 2007 1. This year flow cytometry revealed that the hepatoprotective effects of interleukin (IL)-4 in AILI appeared to be due in part to the regulatory actions of this cytokine on infiltrating neutrophils and monocytes that express IL-4 receptors. 2. This year genome-wide mRNA expression analysis led to the discovery of numerous cellular factors that may play a role in the hepatoprotective effects of IL-13 in AILI. 3. This year we discovered that NK(T) cells played a role in AILI in IL-13 deficient mice, but not in wild type mice suggesting that IL-13 regulates these cells. 4. This year we discovered that endogenous corticosterone released into the blood as a result of hepatocellular injury enhanced the severity of AILI through a mechanism(s) that is mediated by its glucocorticoid receptor. 5. This year we found that stress-induced activation of the mitogen-activated protein kinase, JNK2, protected mice from AILI in part by promoting liver regeneration.