title: Association between TLR4 and PTEN Involved in LPS-TLR4 Signaling Response.
abstract: In this study, we explored the potential mechanisms of how PTEN regulating LPS induced TLR4 signaling pathway. The initial findings from ELISA demonstrate that PTEN influences TNF-α secretion by its lipid phosphatase activity. Subsequently, western blot, immunoprecipitation assay, and immunofluorescence were performed to explore the activation process of PTEN by stimulation with LPS. As early as 20 minutes after LPS stimulation, reduced phosphorylation of PTEN was found obviously. Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS. Moreover, the weak physical association between PTEN and TLR4 in resting RAW264.7 cells increased gradually after the stimulation of LPS. Furthermore, our study showed PTEN decreased LPS-induced Akt activity and upregulated NF-κB-dependent gene transcription, identifying indirectly that the PTEN could regulate the activation of NF-κB by its downstream Akt kinase. In summary, our study illustrates the potential signal transduction process of PTEN while stimulated by LPS: by increasing the association of TLR4, PTEN recruits to its phosphoinositide substrate PI(3,4,5)P3 located on the cell membrane and exerts its dephosphorylated function and subsequently depresses the activity of downstream molecule Akt and results in activation of NF-κB, followed by the secretion of inflammatory mediators TNF-α.
authors: Department of Infection & Immunity, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Huahua
authors: H
authors: Yin
authors: Department of Infection & Immunity, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Yan
authors: Y
authors: Tan
authors: Department of Infection & Immunity, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Xiaofeng
authors: X
authors: Wu
authors: Department of Infection & Immunity, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Hong
authors: H
authors: Yan
authors: Department of Infection & Immunity, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Feng
authors: F
authors: Liu
authors: Department of Trauma, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Yuanzhang
authors: Y
authors: Yao
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Jianxin
authors: J
authors: Jiang
authors: Toronto Western Research Institute, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8.
authors: Qi
authors: Q
authors: Wan
authors: Department of Infection & Immunity, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China; State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China.
authors: Lei
authors: 0000-0003-2834-4633
authors: L
authors: Li
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000276:immunology*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse