title: Both intrinsic and extrinsic apoptotic pathways are involved in Toll-like receptor 4 (TLR4)-induced cell death in monocytic THP-1 cells.
abstract: Our previous study showed that TLR3 induces apoptosis via both death receptors and mitochondial in human endothelial cells. We report here that the activation of TLR4 induced dose- and time-dependent cell death in moncytic THP-1 cells. LPS treatment of THP-1 cells induced the activation of both caspase 8 and 9, suggesting the involvement of intrinsic and extrinsic apoptosis pathways. TNFα was induced by TLR4 activation at both mRNA and protein levels, but its neutralization did not down-regulated TLR4-induced cell death. TLR4 activation also induced the up-regulation of TRAIL and its receptors DR4 and DR5, and the neutralization of TRAIL ameliorated TLR4 induced apoptosis, suggesting the involvement of TRAIL and its receptors DR4 and DR5 in LPS-induced cell death. Meanwhile, LPS treatment down-regulated the expression of FLICE inhibitory protein (FLIP), a suppressor of death receptor-induced cell death. In addition, TLR4 activation down-regulated the anti-apoptotic protein bcl-2, and up-regulated the pro-apoptotic proteins Noxa and Puma, suggesting that mitochondrial apoptotic pathway was also involved in LPS-induced cell death. Furthermore, we found that TAP63α might confer to the activation of intrinsic and extrinsic apoptotic pathways. The treatment of THP-1 cells with LPS induced the translocation of TAP63α from cytoplasm to nucleus. Taken together, our study suggested that both death receptors and mitochondial were involved in TLR4-induced cell death, and TAP63α may be a target for the prevention of LPS-induced cell death.
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, China; Department of Pathology, Affiliated Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, XinXiang Medical University, XinXiang, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Luo
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Liu
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Tuberculosis Research Center, Changsha Central Hospital, Changsha, China. Electronic address: YL7618@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, China. Electronic address: jinyueh@yahoo.com.
authors.forename: Jinyue
authors.initials: J
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D015398:Signal Transduction; D000074084:THP-1 Cells; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C115051:TP63 protein, human; D051197:Toll-Like Receptor 4; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D053181:Caspase 8; D053453:Caspase 9
keywords: Cell death; Death receptor; Mitochondrial; Monocyte; TAp63α; TLR4