Expression data from mouse livers lacking STAT3 during pneumonia

A common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of STAT3 on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia. Using the Cre-LoxP system, mice were generated with functional deletion of STAT3 in hepatocytes. In mutant mice, Cre-recombinase was expressed under transcriptional control of an albumin promoter in the presence of homozygous floxed alleles for STAT3. Wild-type control mice lacked the Cre-recombinase transgene. Microarray analysis was performed on liver RNA collected from both genotypes of mice in the absence and presence of pneumococcal pneumonia. RNA from 2 separate groups of mice (3 mice per group) was analyzed: 1) Control mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3); and 2) Mutant mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3).

生理应激的常见应答为肝脏急性期反应（hepatic acute phase response），该过程中肝脏内众多基因的表达发生改变。其中编码急性期蛋白（acute phase proteins）的转录本（transcripts）亦位列其中，急性期蛋白被定义为在急性期反应过程中浓度发生显著变化的循环蛋白。
本研究旨在明确细菌肺炎期间，信号转导与转录激活因子3（STAT3）对肝脏基因表达变化的影响，此类变化包括但不限于急性期蛋白相关的改变。本研究利用Cre-LoxP重组酶系统（Cre-LoxP system），构建了肝细胞中STAT3功能缺失的小鼠模型。在该突变小鼠中，当携带STAT3的纯合floxed等位基因时，Cre重组酶（Cre-recombinase）会在白蛋白启动子（albumin promoter）的转录调控下表达。野生型对照小鼠则不携带Cre重组酶转基因。
本研究对两种基因型小鼠的肝脏RNA开展基因芯片（Microarray）分析，样本采集自处于肺炎球菌肺炎存在与不存在两种状态下的小鼠。本次分析共纳入两组独立小鼠（每组3只）：1）经气管内接种10^6菌落形成单位（CFU）的3型肺炎链球菌（Streptococcus pneumoniae血清型3）、感染24小时的对照小鼠；2）经气管内接种10^6 CFU的3型肺炎链球菌、感染24小时的突变小鼠。