BACKGROUND Tuberculosis is chronic infection caused by Mycobacterium tuberculosis (M.tb), which infects specifically macrophages. Hif-1, hypoxia-inducible factor-1, was reported to act as master regulator of killing functions in macrophages. AIM To investigate whether Hif-1 activation would enhance bactericidal effect of macrophages and anti-tuberculosis effect of chemical reagent. METHODS Hif-1 and LC3B were detected in tissues from pulmonary tuberculosis. U937, human monocytic leukemia cell line, was stimulated with PMA and differentiated into macrophages. Cells were pretreated with Hif-1 chemical inhibitor YC-1, stimulated with CoCl2 (Hif-1 activator), to detect LC3B with Western blot and confocal microscopy. Cells were infected with M. tb H37Rv strain, stimulated with CoCl2, following rifampine treatment. Expression of autophagy markers was detected using Western blot. IL-6 and TNF-α were detected in cell supernatant with ELISA. Acid-fast staining and CFU assay were performed to evaluate intracellular bacterial load. RESULTS AND CONCLUSIONS Hif-1 and LC3B increased in tissues of pulmonary tuberculosis. Hif-1 activation enhanced autophagy in M. tb infected U937 cells and production of IL-6 and TNF-α. Data from acid-fast staining and CFU indicated that Hif-1 activation enhanced anti-tuberculosis effect of rifampine in macrophages. Conclusively, to activate Hif-1 would strengthen bactericidal effect of macrophages, to further enhance anti-tuberculosis effect of chemical reagent.

中文翻译：

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激活缺氧诱导因子 1 (Hif-1) 增强巨噬细胞对结核分枝杆菌的杀菌作用

背景结核病是由结核分枝杆菌（M.tb）引起的慢性感染，结核分枝杆菌专门感染巨噬细胞。据报道，Hif-1，即缺氧诱导因子-1，是巨噬细胞杀伤功能的主要调节因子。目的探讨Hif-1活化是否会增强巨噬细胞的杀菌作用和化学试剂的抗结核作用。方法在肺结核组织中检测Hif-1和LC3B。U937，人单核细胞白血病细胞系，用PMA刺激并分化成巨噬细胞。细胞用 Hif-1 化学抑制剂 YC-1 预处理，用 CoCl2（Hif-1 激活剂）刺激，用蛋白质印迹和共聚焦显微镜检测 LC3B。在利福平处理后，用 CoCl 2 刺激的 M. tb H37Rv 菌株感染细胞。使用蛋白质印迹检测自噬标志物的表达。ELISA法检测细胞上清液中IL-6和TNF-α。进行抗酸染色和 CFU 测定以评估细胞内细菌负荷。结果与结论肺结核组织中Hif-1和LC3B升高。Hif-1 激活增强了结核分枝杆菌感染的 U937 细胞中的自噬以及 IL-6 和 TNF-α 的产生。来自抗酸染色和 CFU 的数据表明 Hif-1 激活增强了利福平在巨噬细胞中的抗结核作用。综上所述，激活Hif-1会增强巨噬细胞的杀菌作用，进一步增强化学试剂的抗结核作用。结果与结论肺结核组织中Hif-1和LC3B升高。Hif-1 激活增强了结核分枝杆菌感染的 U937 细胞中的自噬以及 IL-6 和 TNF-α 的产生。来自抗酸染色和 CFU 的数据表明 Hif-1 激活增强了利福平在巨噬细胞中的抗结核作用。综上所述，激活Hif-1会增强巨噬细胞的杀菌作用，进一步增强化学试剂的抗结核作用。结果与结论肺结核组织中Hif-1和LC3B升高。Hif-1 激活增强了结核分枝杆菌感染的 U937 细胞中的自噬以及 IL-6 和 TNF-α 的产生。来自抗酸染色和 CFU 的数据表明 Hif-1 激活增强了利福平在巨噬细胞中的抗结核作用。综上所述，激活Hif-1会增强巨噬细胞的杀菌作用，进一步增强化学试剂的抗结核作用。