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

Xiaoling Wu; Guangcun Deng; Xiujing Hao; Yong Li; Jin Zeng; Chunyan Ma; Yulong He; Xiaoming Liu; Yujiong Wang

doi:10.3390/ijms15035045

Back

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

Journal article

Open access

Peer reviewed

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

Xiaoling Wu, Guangcun Deng, Xiujing Hao, Yong Li, Jin Zeng, Chunyan Ma, Yulong He, Xiaoming Liu and Yujiong Wang

International journal of molecular sciences, Vol.15(3), pp.5045-5062

03/21/2014

DOI: 10.3390/ijms15035045

PMCID: PMC3975439

PMID: 24663056

Files and links (1)

url

https://doi.org/10.3390/ijms15035045View

Published (Version of record) Open Access

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.

Animals

Apoptosis

bcl-2-Associated X Protein - metabolism

beta Catenin - metabolism

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

Mycobacterium bovis - physiology

Myeloid Cell Leukemia Sequence 1 Protein - metabolism

Signal Transduction

Tumor Necrosis Factor-alpha - metabolism

Wnt Signaling Pathway

Details

Title: Subtitle: A caspase-dependent pathway is involved in Wnt/β-catenin signaling promoted apoptosis in Bacillus Calmette-Guerin infected RAW264.7 macrophages
Creators: Xiaoling Wu - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Guangcun Deng - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Xiujing Hao - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. haoxiujing@126.com
Yong Li - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Jin Zeng - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Chunyan Ma - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Yulong He - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Xiaoming Liu - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Yujiong Wang - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, 750021, Ningxia, China
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.15(3), pp.5045-5062
DOI: 10.3390/ijms15035045
PMID: 24663056
PMCID: PMC3975439
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Language: English
Date published: 03/21/2014
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984288757202771

Metrics

38 Record Views

63 Times Cited - Web of Science