Mechanisms Of Drug-induced Toxicities

2007年年度报告 1. 今年流式细胞术显示，AILI中白细胞介素（IL）-4的肝脏保护作用似乎部分是由于这种细胞因子对表达IL-4受体的浸润中性粒细胞和单核细胞的调节作用。 2. 今年，全基因组mRNA表达分析发现了许多可能在AILI中IL-13的保肝作用中发挥作用的细胞因子。 3. 今年，我们发现NK（T）细胞在IL-13缺陷小鼠的AILI中发挥作用，但在野生型小鼠中不起作用，这表明IL-13调节这些细胞。 4. 今年我们发现，由于肝细胞损伤而释放到血液中的内源性皮质酮通过其糖皮质激素受体介导的机制增强了AILI的严重程度。 5. 今年，我们发现应激诱导的丝裂原活化蛋白激酶（JNK 2）的活化部分通过促进肝再生来保护小鼠免受AILI的影响。

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.