香烟烟雾提取物诱导的亡导致线粒体DNA释放和支气管上皮细胞的炎症
Kenji Mizumura1, Ryosuke Ozoe1, Yosuke Nemoto1
1Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
概括
通过亡释放的线粒体DNA (mtDNA) 将香烟烟雾引起的线粒体损伤与慢性阻塞性肺病 (COPD) 中的呼吸道炎症联系起来. 细胞外mtDNA通过增加肺细胞中的细胞因子水平来促进炎症.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 慢性阻塞性肺病 (COPD) 涉及呼吸道炎症和肺部结构变化,如肺气.
- 香烟烟雾会导致线粒体损伤,亡 (编程细胞死亡) 和肺气,但其与呼吸道炎症的联系尚不清楚.
- 线粒体DNA (mtDNA) 被研究为潜在的调解者,将线粒体损伤与呼吸道炎症联系起来.
研究的目的:
- 为了研究细胞外mtDNA释放的机制.
- 确定mtDNA作为线粒体损伤和COPD中的呼吸道炎症之间的联系的作用.
- 阐明肺上皮细胞中细胞外mtDNA的促炎作用.
主要方法:
- 人类支气管上皮细胞BEAS-2B暴露于香烟烟雾提取物.
- 使用实时PCR测量了线粒体DNA (mtDNA) 的释放.
- 使用Nec-1抑制了亡;使用线粒体抗氧化剂MitoQ.
- 在mtDNA转染后量化了促炎性细胞因子 (IL-6,IL-8).
主要成果:
- 香烟烟雾提取物诱导了mtDNA转移到细胞质和随后的细胞外释放.
- 丧尸酶抑制和MitoQ减少了细胞外mtDNA释放,但没有影响细胞质转位.
- 细胞外mtDNA显著增加了IL-6和IL-8水平,表明它具有促炎作用.
结论:
- 死体亡在暴露于香烟烟雾后调解细胞外mtDNA的释放,将线粒体损伤与呼吸道炎症联系起来.
- 细胞外mtDNA作为一种促炎媒介,诱导肺上皮细胞中细胞因子的产生.
- 向亡可能为COPD提供治疗策略,解决炎症和肺损伤.
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