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BioMed Research International
Volume 2016, Article ID 6083178, 9 pages
http://dx.doi.org/10.1155/2016/6083178
Research Article

Association between TLR4 and PTEN Involved in LPS-TLR4 Signaling Response

1Department of Infection & Immunity, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China
2Department of Trauma, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Chongqing 400042, China
3State 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
4Toronto Western Research Institute, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8

Received 23 February 2016; Revised 17 May 2016; Accepted 20 June 2016

Academic Editor: Hajime Hisaeda

Copyright © 2016 Huahua Yin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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-B-dependent gene transcription, identifying indirectly that the PTEN could regulate the activation of NF-B 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-B, followed by the secretion of inflammatory mediators TNF-α.