title: Interleukin 17A plays a role in lipopolysaccharide/D-galactosamine-induced fulminant hepatic injury in mice.
abstract: BACKGROUND
  Lipopolysaccharide/d-galactosamine (LPS/GalN)-induced hepatic injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor alpha (TNF-α) plays a pivotal role. Moreover, it was reported from our laboratory that interleukin (IL) 17A enhanced production of TNF-α by the Kupffer cell.
  
  
  OBJECTIVE
  The purpose of this study was to determine the role of IL-17A in LPS/GalN-induced hepatic injury in mice.
  
  
  METHODS
  LPS/GalN was injected into three mouse models: wild-type (WT) mice, IL-17A knockout (KO) mice, or IL-17A KO mice treated with recombinant mouse (rm) IL-17A homodimer (KO + rmIL-17A). Survival was assessed for 24 h after LPS/GalN injection, and histopathologic findings were evaluated at various time points after LPS/GalN injection for neutrophil and apoptosis markers. After LPS/GalN injection, expression of the inflammatory mediators TNF-α, IL-6, monocyte chemotactic protein 1, IL-17A, high-mobility group box 1, and soluble intercellular adhesion molecule 1 was assessed in serum by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Survival was higher in KO mice compared with WT mice after LPS/GalN injection. However, in KO + rmIL-17A mice, mortality was not significantly different compared to the other groups. Neutrophil infiltration and apoptosis were significantly greater in WT mice than KO mice. Furthermore, serum alanine aminotransferase, serum TNF-α, monocyte chemotactic protein 1, IL-17A, high-mobility group box 1, and soluble intercellular adhesion molecule 1 levels were also significantly greater in WT mice than KO mice. In KO + rmIL-17A mice, these levels were similar to those in WT mice.
  
  
  CONCLUSIONS
  IL-17A is a key regulator in hepatic injury caused by neutrophil-induced inflammatory responses after LPS/GalN injection.
authors.affiliation: First Department of Surgery, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Furuya
authors.affiliation: First Department of Surgery, University of Yamanashi, Chuo, Yamanashi, Japan. Electronic address: hkouno@yamanashi.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kono
authors.affiliation: First Department of Surgery, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Hara
authors.affiliation: First Department of Surgery, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirayama
authors.affiliation: First Department of Surgery, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: First Department of Surgery, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D016207:Cytokines / Q000097:blood; D005688:Galactosamine; D024243:HMGB1 Protein / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D020381:Interleukin-17 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology / Q000473:pathology; D017114:Liver Failure, Acute / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D005688:Galactosamine; D000410:Alanine Transaminase
keywords: Fulminant hepatitis; Galactosamine; High-mobility group box 1; Interleukin 6; Interleukin-17A; Lipopolysaccharides; Liver failure; Monocyte chemotactic protein-1; Soluble intercellular adhesion molecule-1; Tumor necrosis factor-alpha