title: Hepatoprotective effects of IL-22 on fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide in mice.
abstract: Interleukin-22 (IL-22), a member of the IL-10 cytokine family that is produced by activated Th22, Th1 and Th17 cells as well as natural killer cells, plays an important role in increase of innate immunity, protection from damage and enhancement of regeneration. Here, we examined the effects of IL-22 on acute liver failure model induced by d-galactosamine (GalN) and lipopolysaccharide (LPS). Administration of recombinant human IL-22 (rhIL-22) reduced the death rate markedly and prevented mice from severe hepatic injury, as evidenced by decreased serum alanine aminotransferase (ALT) and total bilirubin (T.Bil) activity as well as improved histological signs in liver. Furthermore, IL-22 treatment decreased the hepatic malondialdehyde (MDA) contents and increased the reduced glutathione levels. Serum tumor necrosis factor α (TNF-α) level and hepatic caspase-3 activity were significantly lower in mice administrated with IL-22. Moreover, IL-22 treatment significantly enhanced activation of STAT3 and up-regulated the expression of Bcl-xL, heme oxygenase-1 (HO-1) and redox factor-1 (Ref-1) in the liver injury induced by GalN/LPS. Collectively, these data indicate that IL-22 can provide critical protection against GalN/LPS-induced liver injury through anti-apoptotic, anti-oxidant and anti-inflammatory actions.
authors.affiliation: Laboratory of Molecular Genetics, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Xing
authors.forename: Min-ji
authors.initials: MJ
authors.lastname: Zou
authors.forename: Shen
authors.initials: S
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Jia-xi
authors.initials: JX
authors.lastname: Wang
authors.forename: Dong-gang
authors.initials: DG
authors.lastname: Xu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001483:Base Sequence; D001663:Bilirubin / Q000097:blood; D053148:Caspase 3 / Q000097:blood; D017931:DNA Primers; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D005688:Galactosamine / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D007375:Interleukin-1 / Q000097:blood; D007378:Interleukins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D051020:bcl-X Protein / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D000410:Alanine Transaminase; D001663:Bilirubin; D053148:Caspase 3; D017931:DNA Primers; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005688:Galactosamine; D005978:Glutathione; D051547:Heme Oxygenase-1; D007375:Interleukin-1; D007378:Interleukins; D008070:Lipopolysaccharides; D008315:Malondialdehyde; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D000097043:Interleukin-22; C494087:Stat3 protein, mouse; C486216:Apex1 protein, mouse