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.

中文翻译：

---

结核分枝杆菌重组Rv1654蛋白诱导巨噬细胞线粒体介导的凋亡

结核分枝杆菌含有多种免疫活性成分。这项研究调查了新发现的成分 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) 和与 Toll 样受体 4 的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 诱导肿瘤坏死因子-α、白细胞介素- 6，单核细胞趋化蛋白-1通过丝裂原活化蛋白激酶途径。此外，Rv1654 诱导的 c-Jun N 末端激酶 (JNK) 激活被 ROS 清除剂抑制，Rv1654 诱导的细胞凋亡被 JNK 抑制剂抑制。此外，发现用 Rv1654 处理巨噬细胞导致线粒体膜电位的丧失，c进入细胞质，并且 Bax 易位进入线粒体。最后，在用 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。