Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 37, Issue 1, Pages 214-224Publisher
KARGER
DOI: 10.1159/000430346
Keywords
Fulminant hepatitis; Nuclear factor-kappa B; Protein tyrosine phosphatase receptor type O; Toll-like receptor 4
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Funding
- National Natural Science Foundation for Distinguished Young Scholars [81225017]
- National Basic Research Program of China [2012CB910800]
- National Natural Science Foundation [81430062, 81302106, 81201528]
- program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU
- Priority Academic Program of Jiangsu Higher Education Institutions
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Background/Aims: Critical roles of PTPRO and TLR4 have been implicated in hepatocellular carcinoma. However, little is known about their modifying effects on inflammation-related diseases in liver, particularly fulminant hepatitis (FH). We aim to investigate the potential role of PTPRO and its interaction with TLR4 in LPS/D-GaIN induced FH. Methods: A LPS/D-GaIN induced mouse FH model was used. RAW264.7 cells were transfected with PTPRO over-expressed lentiviral plasmids for further investigation. Results: The mortality of PTPRO KO mice is higher than WT mice after LPS/D-GaIN administration. Aggravated liver injury was demonstrated by increased level of serous ALT and AST and numerous hepatic cells death in PTPRO KO mice following LPS/D-GaIN administration. Interestingly, inflammation was attenuated in PTPRO-deficient mice following LPS/D-GaIN administration, which was suggested by decreased inflammatory cytokines (TNF-alpha, IFN-gamma, IL-1 beta, IL-6, IL-17A and IL-12) and cells infiltrating into spleen (CD3(+)IFN-gamma(+) cells, CD3(+)TNF-alpha(+) cells, F4/80(+)VTLR4(+) cells). A feedback regulation between PTPRO and TLR4 dependent on NF-kappa B signaling pathway was demonstrated in vivo and in vitro. Conclusion: PTPRO plays an important role in FH by interacting with TLR4. The crosstalk between PTPRO and TLR4 is a novel bridge linking innate immune and adaptive immune in acute liver injury. Copyright (C) 2015 S. Karger AG, Basel
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