Expression data from mouse livers lacking STAT3 and RelA 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 two transcription factors, STAT3 and NF-kappaB p65 (RelA), on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia. Using the Cre-LoxP system, mice were generated with combined functional deletions of both STAT3 and RelA in hepatocytes. In mutant mice, Cre-recombinase was expressed under transcriptional control of an albumin promoter in the presence of homozygous floxed alleles for both STAT3 and RelA. 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 4 separate groups of mice (3 mice per group) was analyzed: 1) Uninfected wild-type control mice; 2) Uninfected mutant mice lacking liver STAT3 and RelA; 3) Control mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3); and 4) Mutant mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3).机体遭遇生理窘迫时，常见的应答为肝脏急性期应答，该过程中肝脏内众多基因的表达会发生改变。此类转录本中，亦包含编码急性期蛋白的转录本；急性期蛋白被定义为在急性期应答过程中浓度发生显著变化的循环蛋白。本研究旨在明确两种转录因子——信号转导与转录激活因子3（STAT3）与核因子κB p65（RelA）——对细菌性肺炎期间肝脏基因表达变化的影响，相关变化涵盖（但不限于）急性期蛋白相关的基因调控。本研究借助Cre-LoxP重组酶系统，构建了肝细胞内STAT3与RelA双功能缺失的小鼠模型。在突变小鼠中，当STAT3与RelA均为纯合floxed等位基因时，Cre重组酶的表达受白蛋白启动子的转录调控；而野生型对照小鼠则不携带Cre重组酶转基因。研究分别在肺炎链球菌感染与未感染的条件下，采集两种基因型小鼠的肝脏RNA并开展微阵列分析。本次分析共纳入四组独立小鼠样本（每组3只）：1）未感染的野生型对照小鼠；2）未感染且肝脏缺失STAT3与RelA的突变小鼠；3）经气管内接种10^6 CFU 3型肺炎链球菌（Streptococcus pneumoniae serotype 3）并感染24小时的对照小鼠；4）经气管内接种10^6 CFU 3型肺炎链球菌并感染24小时的突变小鼠。