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

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

1
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China
2
College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China
*
Authors to whom correspondence should be addressed.
Received: 28 November 2013 / Revised: 13 February 2014 / Accepted: 10 March 2014 / Published: 21 March 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 Wnt/β-catenin signaling; alveolar macrophages; apoptosis; caspase; mycobacterial infection
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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