非类固醇抗炎药物使上皮细胞对 Clostridioides difficile 毒素介导的线粒体损伤敏感
Joshua Soto Ocaña1,2, Nile U Bayard1, Jessica L Hart1
1Division of Protective Immunity, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Science advances
|July 19, 2023
概括
非类固醇抗炎药物 (NSAIDs) 通过损害结肠细胞,使困难菌感染 (CDI) 恶化. 无抗炎药物和C.C. 困难毒素协同破坏宿主细胞线粒体,加剧感染.
科学领域:
- 微生物学 微生物学
- 胃肠病学 胃肠病学
- 毒理学 毒理学 毒理学
背景情况:
- 艰难菌感染 (CDI) 的发病因子受到生态,免疫和环境因素的影响.
- 制药药物在CDI中的作用尚不清楚,尽管已有证据表明非类固醇抗炎药物 (NSAID) 会使CDI恶化.
- 通过NSAIDs加剧CDI的确切机制尚不清楚.
研究的目的:
- 调查NSAIDs加剧困难菌感染 (CDI) 的机制.
- 为了确定NSAID是否影响结肠上皮细胞 (CECs),以及它们对C的敏感性. 困难的毒素. 有毒物.
- 阐明线粒体损伤在NSAID介导的CDI恶化中的作用.
主要方法:
- 利用结肠上皮细胞 (CEC) 的细胞培养模型.
- 评估了NSAIDs和C的影响. 困难的毒素对CEC活力和线粒体功能.
- 研究了NSAIDs和毒素对细胞损伤的协同作用,独立于循环氧化酶 (COX) 抑制.
主要成果:
- 无 NSAID 药物破坏结肠上皮细胞 (CEC),增加它们对C.的敏感性. 困难的毒素中介损伤. 毒素中介损伤.
- 无论是NSAIDs还是C. 困难的毒素准CEC线粒体.
- 无抗炎药与C.C.有协同作用. 困难的毒素诱导CEC中显著的线粒体损伤,加剧CDI.
结论:
- 无抗炎药物通过直接损害结肠上皮细胞 (CECs) 并使其对毒素敏感,从而加剧困难菌感染 (CDI).
- 恶化的机制涉及NSAIDs和C. 困难毒素协同向并破坏宿主细胞线粒体.
- 这项研究揭示了NSAID诱导结肠微生物感染恶化的新机制.
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