艾滋病毒蛋白酶抑制剂萨基纳维尔通过向受体二分化来抑制类似收费受体4的激活
Kai Yao1, Zheng Wang1, Cheng Peng2
1Department of Vascular Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P. R. China.
Immunopharmacology and immunotoxicology
|July 24, 2023
概括
艾滋病毒药物萨基纳维尔 (SQV) 抑制了托尔类受体4 (TLR4) 信号传递,影响了MyD88和TRIF通路. 这表明SQV可以调节TLR4介导的炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 收费类受体4 (TLR4) 对于天生的免疫力至关重要,识别病原体和内源分子以激活免疫反应.
- TLR4激活涉及连接体诱导的二分化,导致NF-κB和IRF3通过MyD88或TRIF通路发出信号.
- 萨基纳维尔 (SQV) 是一种HIV蛋白酶抑制剂,此前曾显示出抑制TLR4-MyD88关联的潜力.
研究的目的:
- 确定SQV是否是TLR4信号传递的特定抑制剂.
- 为了确定SQV.针对的TLR4的精确信号元件.
- 研究SQV对TLR4介导免疫反应的影响.
主要方法:
- 人类的THP-1巨细胞和HEK293细胞被SQV处理,并用各种TLR激动剂刺激.
- 量化TNF-α水平 (ELISA),NF-κB激活 (SEAP系统) 和MyD88/TRIF通路因子 (免疫块).
- 评估了TLR4内细胞化 (免疫细胞化学),二分化 (免疫沉),并进行了分子对接.
主要成果:
- SQV抑制了由脂聚糖 (LPS) 激活的MyD88和TRIF依赖途径,减少了NF-κB和IRF3.3.
- SQV没有抑制TLR1/2或TLR3通路,这表明特异性.
- 在LPS或HMGB1刺激时,SQV降低了TLR4二分化.
结论:
- TLR4受体复合体是SQV的哺乳动物点.
- SQV可以调节TLR4介导的免疫反应,并可能控制炎症.
- 经FDA批准的SQV提供了一种治疗途径,用于管理TLR4驱动的炎症状况.
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