核酸传感器STING驱动重塑,其抑制提高了慢性阻塞性肺病中的类固醇反应能力
Bushra Mdkhana1, Narjes Saheb Sharif-Askari1,2, Rakhee K Ramakrishnan1
1Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
PloS one
|July 5, 2023
概括
在慢性阻塞性肺病 (COPD) 中,STING通路驱动炎症,类固醇耐药性和重塑. 与类固醇一起抑制STING可能通过逆转这些效应来治疗COPD.
科学领域:
- 免疫学 免疫学 免疫学
- 肺部病理学 肺部病理学
- 细胞生物学 细胞生物学
背景情况:
- 慢性阻塞性肺病 (COPD) 是一种进展性肺病,通常是由香烟烟雾引起的.
- 香烟烟雾可以触发双链DNA释放,激活像STING这样的DNA传感途径.
- 在COPD病原发生过程中,包括炎症,类固醇耐药性和重塑过程中的STING通路的作用需要进一步调查.
研究的目的:
- 分析STING途径在诱导肺炎,类固醇抵抗和COPD重塑中的作用.
- 研究向COPD中的STING途径的治疗潜力.
主要方法:
- 从健康的非吸烟者,健康的吸烟者和COPD个体中分离出初级肺纤维细胞.
- 使用qRT-PCR,西部斑点和ELISA评估了刺痛通路激活,重塑标记物和类固醇耐药性.
- 用德克萨米他和/或STING抑制剂治疗纤维细胞.
主要成果:
- 在健康吸烟者中,STING的表达增加,在COPD纤维细胞中进一步增加.
- 德克萨单一治疗显示COPD纤维细胞的耐药性,而与STING抑制剂的联合治疗是有效的.
- STING刺激增加了重塑标志物并降低了HDAC2;联合疗法通过上调HDAC2.2缓解了重塑并逆转了类固醇耐药性.
结论:
- 刺痛通路对COPD的发病有显著的贡献,导致炎症,类固醇耐药性和重塑.
- 当与COPD的标准类固醇治疗相结合时,STING抑制剂可能作为潜在的治疗辅助剂.
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