AMPK激活通过调节皮肤中的IκBζ表达来调节IL-36诱导的炎症反应
Yi-Ting Huang1, Ling-Ya Chiu1,2, Po-Hsuan Lu3,4
1Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
British journal of pharmacology
|March 27, 2024
概括
AMP激活蛋白激酶 (AMPK) 激活通过减少炎症性细胞因子的释放来抑制IL-36诱导的皮肤炎症. 这表明AMPK激活是IL-36介导炎症性皮肤疾病的潜在治疗策略.
科学领域:
- 皮肤病学 皮肤病学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 介质素 (IL) -36通路与性牛皮病原发生有关.
- 目前针对IL-36的治疗方法有限或昂贵.
- 在IL-36引起的皮肤炎症中AMP激活蛋白激酶 (AMPK) 的作用尚不清楚.
研究的目的:
- 研究AMPK信号传导在调节皮肤IL-36诱导反应中的作用.
- 探索AMPK激活作为IL-36介导的皮肤炎症的潜在治疗策略.
主要方法:
- 主要正常的人类表皮角质细胞 (NHEKs) 和BALB/c小鼠被用作模型.
- 在体外和体内使用IL-36刺激.
- 他们使用了AMPK激活剂,5-aminoimidazole-4-carboxamide riboside (AICAR) 和A769662.
主要成果:
- 在NHEK中,AMPK激活剂抑制了IL-36诱导的IL-8和CCL20产生.
- AMPK激活减少了IL-36诱导的IκBζ表达和IKK/IκBα酸化.
- 在小鼠的局部AICAR应用减少了耳朵胀,红色和炎症基因表达.
结论:
- AMPK激活有效抑制IL-36诱导的皮肤炎症.
- 在角质细胞中IκBζ表达的调节是一个关键的机制.
- AMPK激活为IL-36介导的炎症性皮肤疾病提供了一个有前途的治疗途径.
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