title: Mycobacterium avium MAV2052 protein induces apoptosis in murine macrophage cells through Toll-like receptor 4.
abstract: Mycobacterium avium and its sonic extracts induce apoptosis in macrophages. However, little is known about the M. avium components regulating macrophage apoptosis. In this study, using multidimensional fractionation, we identified MAV2052 protein, which induced macrophage apoptosis in M. avium culture filtrates. The recombinant MAV2052 induced macrophage apoptosis in a caspase-dependent manner. The loss of mitochondrial transmembrane potential (ΔΨm), mitochondrial translocation of Bax, and release of cytochrome c from mitochondria were observed in macrophages treated with MAV2052. Further, reactive oxygen species (ROS) production was required for the apoptosis induced by MAV2052. In addition, ROS and mitogen-activated protein kinases were involved in MAV2052-mediated TNF-α and IL-6 production. ROS-mediated activation of apoptosis signal-regulating kinase 1 (ASK1)-JNK pathway was a major signaling pathway for MAV2052-induced apoptosis. Moreover, MAV2052 bound to Toll-like receptor (TLR) 4 molecule and MAV2052-induced ROS production, ΔΨm loss, and apoptosis were all significantly reduced in TLR4(-/-) macrophages. Altogether, our results suggest that MAV2052 induces apoptotic cell death through TLR4 dependent ROS production and JNK pathway in murine macrophages.
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Kang-In
authors: KI
authors: Lee
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Han-Gyu
authors: HG
authors: Choi
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Yeo-Jin
authors: YJ
authors: Son
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Jake
authors: J
authors: Whang
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Kwangwook
authors: K
authors: Kim
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Heat Sal
authors: HS
authors: Jeon
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Hye-Soo
authors: HS
authors: Park
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Yong Woo
authors: YW
authors: Back
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Seunga
authors: S
authors: Choi
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Seong-Woo
authors: SW
authors: Kim
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors: Chul Hee
authors: CH
authors: Choi
authors: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 301-747, Republic of Korea. hjukim@cnu.ac.kr.
authors: Hwa-Jung
authors: HJ
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009162:Mycobacterium avium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C494827:Bax protein, mouse; D015850:Interleukin-6; C000612728:MAV2052 protein, Mycobacterium avium; D017382:Reactive Oxygen Species; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse
keywords: Apoptosis; MAV2052; Macrophage; Mycobacterium avium complex