Int. J. Mol. Sci. 2014, 15(3), 5045-5062; doi:10.3390/ijms15035045
Article

A Caspase-Dependent Pathway Is Involved in Wnt/β-Catenin Signaling Promoted Apoptosis in Bacillus Calmette-Guerin Infected RAW264.7 Macrophages

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Received: 28 November 2013; in revised form: 13 February 2014 / Accepted: 10 March 2014 / Published: 21 March 2014
(This article belongs to the Section Molecular Pathology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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.
Keywords: Wnt/β-catenin signaling; alveolar macrophages; apoptosis; caspase; mycobacterial infection
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MDPI and ACS Style

Wu, X.; Deng, G.; Hao, X.; Li, Y.; Zeng, J.; Ma, C.; He, Y.; Liu, X.; Wang, Y. A Caspase-Dependent Pathway Is Involved in Wnt/β-Catenin Signaling Promoted Apoptosis in Bacillus Calmette-Guerin Infected RAW264.7 Macrophages. Int. J. Mol. Sci. 2014, 15, 5045-5062.

AMA Style

Wu X, Deng G, Hao X, Li Y, Zeng J, Ma C, He Y, Liu X, Wang Y. A Caspase-Dependent Pathway Is Involved in Wnt/β-Catenin Signaling Promoted Apoptosis in Bacillus Calmette-Guerin Infected RAW264.7 Macrophages. International Journal of Molecular Sciences. 2014; 15(3):5045-5062.

Chicago/Turabian Style

Wu, Xiaoling; Deng, Guangcun; Hao, Xiujing; Li, Yong; Zeng, Jin; Ma, Chunyan; He, Yulong; Liu, Xiaoming; Wang, Yujiong. 2014. "A Caspase-Dependent Pathway Is Involved in Wnt/β-Catenin Signaling Promoted Apoptosis in Bacillus Calmette-Guerin Infected RAW264.7 Macrophages." Int. J. Mol. Sci. 15, no. 3: 5045-5062.


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