A caspase-dependent pathway is involved in Wnt/β-catenin signaling promoted apoptosis in Bacillus Calmette-Guerin infected RAW264.7 macrophages

• Published in: International journal of molecular sciences 2014-03, Vol.15 (3), p.5045-5062
• Main Authors: Wu, Xiaoling, Deng, Guangcun, Hao, Xiujing, Li, Yong, Zeng, Jin, Ma, Chunyan, He, Yulong, Liu, Xiaoming, Wang, Yujiong
• Format: Article
• Language: English
• Subjects: alveolar macrophages; Animals; Apoptosis; bcl-2-Associated X Protein - metabolism; beta Catenin - metabolism; caspase; Caspase 3 - metabolism; Caspases - metabolism; Cell Line; Flow Cytometry; Host-Pathogen Interactions; Immunoblotting; Interleukin-6 - metabolism; Macrophages - metabolism; Macrophages - microbiology; Macrophages - ultrastructure; Membrane Potential, Mitochondrial; Mice; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; mycobacterial infection; Mycobacterium bovis; Mycobacterium bovis - physiology; Mycobacterium tuberculosis; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Signal Transduction; Tumor Necrosis Factor-alpha - metabolism; Wnt Signaling Pathway; Wnt/β-catenin signaling
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms15035045

Apoptosis of alveolar macrophages following Mycobacterium tuberculosis infection have been demonstrated to play a central role in the pathogenesis of tuberculosis. In the present study, we found that Wnt/β-catenin signaling possesses the potential to promote macrophage apoptosis in response to mycobacterial infection. In agreement with other findings, an activation Wnt/β-catenin signaling was observed in murine macrophage RAW264.7 cells upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection at a multiple-of-infection of 10, which was accompanied with up-regulation of pro-inflammatory cytokines TNF-α and IL-6 production. However, the BCG-induced TNF-α and IL-6 secretion could be significantly reduced when the cells were exposed to a canonical Wnt signaling ligand, Wnt3a. Importantly, the activation of Wnt/β-catenin signaling was able to further promote apoptosis in BCG-infected RAW264.7 cells in part by a mitochondria-dependent apoptosis pathway. Immunoblotting analysis further demonstrated that Wnt/β-catenin signaling-induced cell apoptosis partly through a caspase-dependent apoptosis mechanism by down-regulation of anti-apoptotic protein Mcl-1, and up-regulation of pro-apoptotic proteins Bax and cleaved-caspase-3, as well as enhancement of caspase-3 activity in BCG-infected RAW264.7 cells. These data may imply an underlying mechanism of alveolar macrophages in response to mycobacterial infection, by which the pathogen induces Wnt/β-catenin signaling activation, which in turn represses mycobacterium-trigged inflammatory responses and promotes mycobacteria-infected cell apoptosis.