title: Aggravated Liver Injury but Attenuated Inflammation in PTPRO-Deficient Mice Following LPS/D-GaIN Induced Fulminant Hepatitis.
abstract: OBJECTIVE
  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-α, IFN-γ, IL-1β, IL-6, IL-17A and IL-12) and cells infiltrating into spleen (CD3(+)IFN-γ(+) cells, CD3(+)TNF-α(+) cells, F4/80(+)/TLR4(+) cells). A feedback regulation between PTPRO and TLR4 dependent on NF-κB signaling pathway was demonstrated in vivo and in vitro.
  
  
  CONCLUSIONS
  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.
authors: Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Xiaochen
authors: X
authors: Wang
authors: Shushan
authors: S
authors: Yan
authors: Donghua
authors: D
authors: Xu
authors: Jun
authors: J
authors: Li
authors: Yu
authors: Y
authors: Xie
authors: Jiajie
authors: J
authors: Hou
authors: Runqiu
authors: R
authors: Jiang
authors: Chuanyong
authors: C
authors: Zhang
authors: Beicheng
authors: B
authors: Sun
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005688:Galactosamine / Q000494:pharmacology*; D006505:Hepatitis / Q000378:metabolism* / Q000473:pathology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000172:deficiency*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D005688:Galactosamine; C516890:Ptpro protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3