title: Interleukin-17A plays a pivotal role after partial hepatectomy in mice.
abstract: BACKGROUND
  Liver regeneration after partial hepatectomy (PH) is regulated by tumor necrosis factor (TNF)-α derived from the Kupffer cell. Furthermore, it was reported from our laboratory that interleukin (IL)-17A enhances the production of TNF-α by the Kupffer cell, suggesting that IL-17A may play a role in liver regeneration.
  
  
  OBJECTIVE
  The purpose was to determine the role of IL-17A and the spleen in liver regeneration after PH.
  
  
  METHODS
  Two mouse models including the wild-type (WT) mice or the IL-17A knockout (KO) mice underwent PH. Animals were killed at the designated time points; liver tissues were harvested for further investigation. Proliferation of hepatocytes was evaluated. Furthermore, the messenger RNA and protein expression of TNF-α and IL-6 were measured in the liver. In another set of experiments, the two animal models underwent splenectomy before PH. In an in vitro study, CD4-positive lymphocytes in the spleen were isolated from mice, and the number of IL-17A-positive cells was investigated.
  
  
  RESULTS
  Liver regeneration was significantly impaired in the KO mice compared with the WT mice. This was associated with suppression of cell proliferation assessed by cell proliferation markers in the KO mice. In the WT mice that underwent splenectomy, liver regeneration was significantly delayed compared with animals without splenectomy. In contrast, splenectomy did not affect liver regeneration in the KO mice. IL-17A-positive lymphocytes increased significantly in the spleen in the WT mice after PH.
  
  
  CONCLUSIONS
  These results indicate that IL-17A derived from CD4-positive lymphocytes in the spleen is a key regulator in liver regeneration after PH.
authors.affiliation: First Department of Surgery, University of Yamanashi, Yamanashi, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Furuya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kono
authors.forename: Michio
authors.initials: M
authors.lastname: Hara
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirayama
authors.forename: Masato
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D049109:Cell Proliferation; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000473:pathology; D066298:In Vitro Techniques; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D008099:Liver / Q000473:pathology / Q000502:physiology* / Q000601:surgery*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D013154:Spleen / Q000473:pathology / Q000502:physiology / Q000601:surgery; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Cytokine; Interleukin-17A; Interleukin-17A knockout mouse; Kupffer cell; Partial hepatectomy; Spleen; Splenectomy