Infectious Disease Division, Memorial Hospital of Rhode Island, Warren Alpert School of Medicine of Brown University, Providence, Rhode Island, USA.
J Infect Dis. 2010 Apr 15;201(8):1250-7. doi: 10.1086/651276.
Nonsteroidal agonists have been developed that selectively bind to and activate estrogen receptor beta (ERbeta) rather than estrogen receptor alpha (ERalpha). ERbeta is expressed equally in both male and female mammals in multiple extragonadal tissues. Work reported elsewhere has demonstrated that ERbeta agonists have beneficial effects in multiple (but not all) models of inflammatory diseases and also increase survival in experimentally induced sepsis.
In these experiments, ERbeta agonists (ERB-041 or WAY-202196) were compared with vehicle control in the murine cecal ligation and puncture (CLP) model and in the pneumococcal pneumonia model of sepsis. The effect of WAY-202196 on the gene expression profile in the CLP model was further studied by transcriptome analysis of lung and small intestine tissue samples.
ERbeta agonists provided a significant survival benefit in both experimental models of bacterial sepsis. This survival advantage was accompanied by reduced histologic evidence of tissue damage, reduced transcription of multiple proinflammatory proteins by transcriptome analysis and was not associated with increased bacterial outgrowth.
ERbeta agonist administration provided a survival advantage in septic animals and appears to be a promising therapeutic modality in sepsis.
已经开发出了非甾体激动剂，它们可以选择性地与雌激素受体β（ERβ）结合并激活，而不是与雌激素受体α（ERα）结合。ERβ在雄性和雌性哺乳动物的多种外胚层组织中表达水平相等。其他地方的研究工作表明，ERβ激动剂对多种（但不是所有）炎症性疾病模型具有有益作用，并且还可以提高实验性诱导性败血症的存活率。
在这些实验中，将 ERβ激动剂（ERB-041 或 WAY-202196）与载剂对照在小鼠盲肠结扎和穿孔（CLP）模型以及细菌性败血症的肺炎球菌肺炎模型中进行比较。通过对 CLP 模型中肺和小肠组织样本的转录组分析，进一步研究了 WAY-202196 对 CLP 模型中基因表达谱的影响。
ERβ激动剂在两种细菌性败血症的实验模型中均提供了显著的生存获益。这种生存优势伴随着组织损伤的组织学证据减少，转录组分析中多个促炎蛋白的转录减少，并且与细菌生长增加无关。
ERβ激动剂的给予在败血症动物中提供了生存优势，并且似乎是败血症的一种有前途的治疗方式。
