title: Interleukin-17A Plays a Pivotal Role in Chemically Induced Hepatocellular Carcinoma in Mice.
abstract: OBJECTIVE
  The aim of the present study was to investigate the role of interleukin (IL)-17A in the initiation and progression of hepatocellular carcinoma.
  
  
  METHODS
  IL-17A deficient (KO) and wild-type (WT) mice were intraperitoneal injected with diethyl nitrosamine (DEN) to induce hepatocellular carcinoma, and the incidence of tumours was assessed 38 weeks later. In order to investigate the effects of DEN on hepatocytes in the acute phase of DEN administration, DEN-treated mice were sacrificed at designated time points. Serum and liver tissues were harvested for further analyses.
  
  
  RESULTS
  The tumor incidence was approximately 65 % in WT mice, but was significantly lower (by 20 %) in KO mice. The number of tumours was also less in KO mice. Serum ALT levels increased in WT mice 7 days after the administration of DEN, but were significantly lower in KO mice. Furthermore, the number of neutrophils and Kupffer cells, and the expression of TNF-α and IL-6 were reduced in KO mice. The intrahepatic expression of the oxidative DNA damage marker 8-OHdG and lipid oxidative marker 4-HNE was markedly increased in WT mice, but was significantly lower in KO mice. In addition, the increase of cell proliferation, as assessed by Ki-67 immunohistochemistry, in WT mice was significantly reduced in KO mice.
  
  
  CONCLUSIONS
  These results demonstrated that IL-17A plays a pivotal role in chemically induced hepatic carcinogenesis, which is most likely through inflammation-initiated oxidative DNA damage and cell proliferation.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kono
authors.forename: Shinji
authors.initials: S
authors.lastname: Furuya
authors.forename: Michio
authors.initials: M
authors.lastname: Hara
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirayama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Akazawa
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Nakata
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004052:Diethylnitrosamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine