这项研究的目的是测试重组小鼠(mo)PrP单独或与LPS组合或在模拟内毒素血症下是否会影响与宿主炎症和抗微生物反应相关的基因的表达。为了测试我们的假设,从16只雄性小鼠(FVB/N品系)收集结肠组织并将其安装在Ussing室中。将moPrP应用于结肠粘膜侧影响与TLR和NLR信号传导和抗微生物反应相关的基因。当在结肠粘膜侧加入LPS时,与TLR相关的基因,Nlrp3炎性体,和铁转运蛋白过度表达。将LPS添加到与TLR和NLR信号相关的结肠浆膜侧上调基因,Nlrp3炎性体,和趋化因子.用moPrP和LPS治疗结肠粘膜侧上调与TLR相关的基因,下游信号转导(DST),炎症反应,树突状细胞对炎症部位的吸引,和JNK-凋亡途径。对粘膜侧施用moPrP,对结肠浆膜侧施用LPS,影响与TLR和NLR信号相关的基因,DST,凋亡,炎症反应,细胞因子,趋化因子,和抗菌肽。总的来说,这项研究表明moPrP作为内源性“危险信号”的潜在作用,与先天免疫和抗菌反应相关的结肠基因的激活有关。
The objectives of this study were to test whether recombinant mouse (mo)PrP alone or in combination with LPS or under simulated endotoxemia would affect expression of genes related to host inflammatory and antimicrobial responses. To test our hypotheses colon tissues were collected from 16 male mice (FVB/N strain) and mounted in an Ussing chamber. Application of moPrP to the mucosal side of the colon affected genes related to TLR- and NLR- signaling and antimicrobial responses. When LPS was added on the mucosal side of the colon, genes related to TLR, Nlrp3 inflammasome, and iron transport proteins were over-expressed. Addition of LPS to the serosal side of the colon up-regulated genes related to TLR- and NLR-signaling, Nlrp3 inflammasome, and a chemokine. Treatment with both moPrP and LPS to the mucosal side of the colon upregulated genes associated with TLR, downstream signal transduction (DST), inflammatory response, attraction of dendritic cells to the site of inflammation, and the JNK-apoptosis pathway. Administration of moPrP to the mucosal side and LPS to the serosal side of the colon affected genes related to TLR- and NLR-signaling, DST, apoptosis, inflammatory response, cytokines, chemokines, and antimicrobial peptides. Overall this study suggests a potential role for moPrP as an endogenous \'danger signal\' associated with activation of colon genes related to innate immunity and antibacterial responses.