title: A caspase-dependent pathway is involved in Wnt/β-catenin signaling promoted apoptosis in Bacillus Calmette-Guerin infected RAW264.7 macrophages.
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.
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. nx_wuxiaol@163.com.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. nx_dgc@163.com.
authors.forename: Guangcun
authors.initials: G
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Xiujing
authors.initials: X
authors.lastname: Hao
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. liyong7732@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. zengjinnxu@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. machnyan0411@163.com.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ma
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. heyulong2003@163.com.
authors.forename: Yulong
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. lxm1966@nxu.edu.cn.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan 750021, Ningxia, China. wyj@nxu.edu.cn.
authors.forename: Yujiong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D015151:Immunoblotting; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009163:Mycobacterium bovis / Q000502:physiology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C494827:Bax protein, mouse; D015850:Interleukin-6; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; D053148:Caspase 3; D020169:Caspases