Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites.
Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites.
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DOI：
10.1016/j.bbrc.2013.02.002
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发表时间：
2013-03-08
影响因子：
3.1
通讯作者：
de Camargo, Maristela M.
中科院分区：
文献类型：
--
作者：
Bonin, Camila P.;Baccarin, Raquel Y. A.;Nostell, Katarina;Nahum, Laila A.;Fossum, Caroline;de Camargo, Maristela M.
Toll样受体4（TLR4）与脂多糖（LPS）的结合是脓毒性休克有害作用的主要触发因素。马和人类被认为是感染性休克最敏感的物种，但解释这些现象的机制仍然难以捉摸。对tlr4启动子的分析显示，LPS敏感物种（人、黑猩猩和马）之间的相似性很高，而与LPS抗性物种（小鼠和大鼠）的相似性很低。在tlr 4启动子和md2启动子序列中发现了4个保守的核因子κ B（NFκB）结合位点，可能是地塞米松调控的靶点。用LPS体外处理马外周血单核细胞（eqPBMC）降低了tlr4的转录，增加了md2（髓样分化因子2）和cd14（分化簇14）的转录。地塞米松治疗挽救了LPS抑制后tlr4的转录。LPS诱导的md2转录在地塞米松的存在下被抑制。地塞米松单独使用不影响tlr4和md2的转录。
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.
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DOI：
10.1084/jem.189.11.1777
发表时间：
1999-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Shimazu R;Akashi S;Ogata H;Nagai Y;Fukudome K;Miyake K;Kimoto M
通讯作者：
Kimoto M
影响因子：
56.9
作者：
SCHUMANN, RR;LEONG, SR;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
56.9
作者：
WRIGHT, SD;RAMOS, RA;MATHISON, JC
通讯作者：
MATHISON, JC
影响因子：
4.4
作者：
Medvedev, AE;Henneke, P;Vogel, SN
通讯作者：
Vogel, SN
影响因子：
120.7
作者：
RANGELFRAUSTO, MS;PITTET, D;WENZEL, RP
通讯作者：
WENZEL, RP