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- Title
A Caspase-Dependent Pathway Is Involved in Wnt/ß-Catenin Signaling Promoted Apoptosis in Bacillus Calmette-Guerin Infected RAW264.7 Macrophages.
- Authors
Xiaoling Wu; Guangcun Deng; Xiujing Hao; Yong Li; Jin Zeng; Chunyan Ma; Yulong He; Xiaoming Liu; Yujiong Wang
- 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/ß-catenin signaling possesses the potential to promote macrophage apoptosis in response to mycobacterial infection. In agreement with other findings, an activation Wnt/ß-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-a and IL-6 production. However, the BCG-induced TNF-a 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/ß-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/ß-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/ß-catenin signaling activation, which in turn represses mycobacterium-trigged inflammatory responses and promotes mycobacteria-infected cell apoptosis.
- Subjects
CASPASES; CATENINS; APOPTOSIS; BCG vaccines; MACROPHAGES; MYCOBACTERIUM bovis
- Publication
International Journal of Molecular Sciences, 2014, Vol 15, Issue 3, p5045
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms15035045