核受体和通道式受体之间的交叉声调的分子决定因素
Sumito Ogawa1, Jean Lozach, Chris Benner
1Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
核受体 (NR) 通过抑制炎症基因来控制免疫反应. 葡萄糖皮质体受体 (GR) 和其他NRs特别向通用类似受体 (TLR) 途径,为炎症提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 核受体 (NRs) 是基因表达的关键调节者.
- NRs调节各种信号通路,包括免疫反应.
- NR介导的基因抑制 (转抑制) 的机制尚未完全理解.
研究的目的:
- 研究NRs的信号和基因特异性转压.
- 阐明NR机制在调节巨细胞中类似收费受体 (TLR) 信号传递中的作用.
- 探索炎症性疾病的治疗潜力.
主要方法:
- 研究了巨细胞中TLR3,TLR4和TLR9信号的抑制.
- 研究了葡萄糖皮质体受体 (GR),PPARgamma和LXRs的作用.
- 分析了转录因子复合体 (p65/IRF) 的破坏.
主要成果:
- GR 通过 p65/IRF 干扰,特别抑制 TLR4/TLR9 依赖的炎症基因,独立于 TLR3.
- GR的机制需要MyD88信号来对病原体特异性基因程序进行差异调节.
- PPARgamma和LXR与GR合作,通过p65/IRF独立的通路协同抑制不同的TLR响应基因.
结论:
- NRs对免疫平衡和炎症反应表现出组合控制.
- NRs提供了TLR诱导的转录的信号和基因特异性调节.
- 研究结果表明,通过调节NR活性,可以为炎症性疾病提供新的治疗点.
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