脂多糖体外诱导的 TLR4 转录抑制可被地塞米松逆转，并与保守的 NFκB 结合位点的存在相关。
Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites.
机构信息
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil.
出版信息
Biochem Biophys Res Commun. 2013 Mar 8;432(2):256-61. doi: 10.1016/j.bbrc.2013.02.002. Epub 2013 Feb 10.
Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2.
Toll 样受体 4（TLR4）与脂多糖（LPS）的结合是脓毒性休克有害效应的主要触发因素。马和人类被认为是对脓毒性休克最敏感的物种，但解释这些现象的机制仍不清楚。对 tlr4 启动子的分析表明，LPS 敏感物种（人类、黑猩猩和马）之间具有高度相似性，而 LPS 抗性物种（小鼠和大鼠）之间则具有较低的相似性。在 tlr4 启动子和 md2 启动子序列中发现了四个保守的核因子 kappa B（NFκB）结合位点，这些位点可能是地塞米松调节的靶标。体外用 LPS 处理马外周血单核细胞（eqPBMC）后，tlr4 的转录物减少，md2（髓样分化因子 2）和 cd14（分化簇 14）的转录增加。地塞米松处理可挽救 LPS 抑制后 tlr4 的转录。地塞米松存在时，LPS 诱导的 md2 转录受到抑制。地塞米松单独处理对 tlr4 和 md2 的转录没有影响。
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