Zhou Diana X, Zhao Yinghong, Baker Jessica A, Gu Qingqing, Hamre Kristin M, Yue Junming, Jones Byron C, Cook Melloni N, Lu Lu
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
PLoS One. 2017 Jun 2;12(6):e0178689. doi: 10.1371/journal.pone.0178689. eCollection 2017.
Alcohol consumption affects human health in part by compromising the immune system. In this study, we examined the expression of the Cd14 (cluster of differentiation 14) gene, which is involved in the immune system through a proinflammatory cascade. Expression was evaluated in BXD mice treated with saline or acute 1.8 g/kg i.p. ethanol (12.5% v/v). Hippocampal gene expression data were generated to examine differential expression and to perform systems genetics analyses. The Cd14 gene expression showed significant changes among the BXD strains after ethanol treatment, and eQTL mapping revealed that Cd14 is a cis-regulated gene. We also identified eighteen ethanol-related phenotypes correlated with Cd14 expression related to either ethanol responses or ethanol consumption. Pathway analysis was performed to identify possible biological pathways involved in the response to ethanol and Cd14. We also constructed a genetic network for Cd14 using the top 20 correlated genes and present several genes possibly involved in Cd14 and ethanol responses based on differential gene expression. In conclusion, we found Cd14, along with several other genes and pathways, to be involved in ethanol responses in the hippocampus, such as increased susceptibility to lipopolysaccharides and neuroinflammation.
酒精消费部分地通过损害免疫系统来影响人类健康。在本研究中，我们检测了Cd14（分化簇14）基因的表达，该基因通过促炎级联反应参与免疫系统。在用生理盐水或1.8 g/kg腹腔注射乙醇（12.5% v/v）急性处理的BXD小鼠中评估表达情况。生成海马体基因表达数据以检查差异表达并进行系统遗传学分析。乙醇处理后，Cd14基因表达在BXD品系间显示出显著变化，并且表达数量性状位点定位表明Cd14是一个顺式调控基因。我们还鉴定出18种与乙醇反应或乙醇消费相关的、与Cd14表达相关的乙醇相关表型。进行通路分析以确定参与乙醇反应和Cd14反应的可能生物学通路。我们还使用排名前20的相关基因构建了Cd14的遗传网络，并基于差异基因表达呈现了几个可能参与Cd14和乙醇反应的基因。总之,我们发现Cd14以及其他几个基因和通路参与海马体中的乙醇反应，比如对脂多糖和神经炎症的易感性增加。
