皮奥格利塔逆转酒精诱导的HIV复制和IL-1β表达在膜巨细胞
Moses New-Aaron1, Sarah S Chang2, Xian Fan3
1Emory University School of Medicine, Pulmonary, Allergy, Critical Care and Sleep Medicine, Atlanta, Georgia, United States.
American journal of respiratory cell and molecular biology
|April 30, 2025
概括
酒精代谢物乙甲恶化HIV复制和巨细胞中的肺炎. 皮奥格利塔治疗减少了这些影响,为艾滋病毒患者滥用酒精和肺部问题提供了潜在的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 药理学 药理学是指药理学的学科.
背景情况:
- 艾滋病毒感染者 (PWH) 经常滥用酒精,增加患慢性肺炎的风险.
- 乙甲是一种酒精代谢物,在体内循环,向肺膜巨细胞 (AMs),这是肺部的关键HIV储存库.
- 乙甲基可促进艾滋病毒的复制和在AMS中释放互白素 (IL) - 1β.
研究的目的:
- 为了研究酒精衍生的乙甲如何驱动HIV复制和IL-1β在AMS中的释放.
- 为了确定皮奥格利塔 (pioglitazone) 是否可以降低 AM HIV 复制和 IL-1β 释放.
主要方法:
- 使用初级小鼠AMs,AM细胞系 (MH-S) 和人类单细胞衍生的巨细胞 (THP-1).
- 细胞使用乙甲生成系统 (AGS),HIV 1ADA和EcoHIV进行了治疗.
- 测量了艾滋病毒的表达,IL-1β水平,过氧化 (H2O2) 的释放,以及蛋白质水平 (ERK1/2,PPARγ,NF-B/p65).
主要成果:
- 乙甲显著增加了H2O2的释放,导致ERK1/2酸化和PPARγ失活.
- 乙甲促进了HIV感染细胞中NF-B/p65的核转移,增强了HIV复制和IL-1β释放.
- 皮奥格利塔治疗降低了核p65,从而降低了乙甲诱导的HIV复制和IL-1β激活.
结论:
- 乙甲通过一种涉及H2O2,ERK1/2,PPARγ和NF-B/p65.5的机制来增强艾滋病毒复制和AMs中的炎症激活.
- 皮奥格利塔可以减轻这些影响,这表明它在滥用酒精的人群中治疗与艾滋病毒相关的呼吸道并发症的治疗潜力.
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