Recombinant Rv1654 Protein of Mycobacterium tuberculosis Induces Mitochondria-Mediated Apoptosis in Macrophages.

Mycobacterium tuberculosis contains diverse immunologically active components. In this study, we investigated the biological function of a newly identified component, Rv1654, with potential to induce apoptosis in macrophages. Recombinant Rv1654 induced macrophage apoptosis in a caspase-9/3-dependent manner through reactive oxygen species (ROS) production and interaction with Toll-like receptor 4. In addition, Rv1654 induced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production 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, we found that treatment of macrophages with Rv1654 led to 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. This article is protected by copyright. All rights reserved.