Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, South Korea.
Department of Translational Immunology Institute, College of Medicine, Chungnam National University, Daejeon, South Korea.
Microbiol Immunol. 2021 Apr;65(4):178-188. doi: 10.1111/1348-0421.12880. Epub 2021 Mar 24.
Mycobacterium tuberculosis contains diverse immunologically active components. This study investigated the biological function of a newly identified component, Rv1654, with the potential to induce apoptosis in macrophages. Recombinant Rv1654 induced macrophage apoptosis in a caspase-9/3-dependent manner through the production of reactive oxygen species (ROS) and interaction with Toll-like receptor 4. In addition, Rv1654 induced the production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 through the mitogen-activated protein kinase pathway. Furthermore, Rv1654-induced c-Jun N-terminal kinase (JNK) activation was inhibited by the ROS scavenger and Rv1654-induced apoptosis was inhibited by the JNK inhibitor. Moreover, it was found that treatment of macrophages with Rv1654 led to the loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, and translocation of Bax into the mitochondria. Finally, Rv1654-mediated apoptosis was inhibited in macrophages transfected with Bax siRNA. These results suggest that Rv1654 induces macrophage apoptosis through a mitochondrial-dependent pathway and ROS-mediated JNK activation.
结核分枝杆菌含有多种免疫活性成分。本研究探讨了一种新鉴定的成分 Rv1654 的生物学功能，该成分具有诱导巨噬细胞凋亡的潜力。重组 Rv1654 通过产生活性氧（ROS）并与 Toll 样受体 4 相互作用，以半胱天冬酶-9/3 依赖性方式诱导巨噬细胞凋亡。此外，Rv1654 通过丝裂原活化蛋白激酶途径诱导肿瘤坏死因子-α、白细胞介素-6 和单核细胞趋化蛋白-1 的产生。此外，ROS 清除剂抑制 Rv1654 诱导的 c-Jun N 端激酶（JNK）激活，JNK 抑制剂抑制 Rv1654 诱导的细胞凋亡。此外，还发现用 Rv1654 处理巨噬细胞会导致线粒体膜电位丧失、细胞色素 c 释放到细胞质中和 Bax 易位到线粒体中。最后，用 Bax siRNA 转染的巨噬细胞中 Rv1654 介导的细胞凋亡受到抑制。这些结果表明，Rv1654 通过线粒体依赖性途径和 ROS 介导的 JNK 激活诱导巨噬细胞凋亡。
