title: Kupffer cells contribute to concanavalin A-induced hepatic injury through a Th1 but not Th17 type response-dependent pathway in mice.
abstract: BACKGROUND
  Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice, but the underlying mechanisms remain obscure. The present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice, and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway.
  
  
  METHODS
  Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A. Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A injection. The interferon-gamma (IFN-gamma) and interleukin-17 (IL-17) pathways were blocked by specific neutralizing antibodies. Hepatic injury was assessed using serum transferase activity and pathological analysis. Expression of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry.
  
  
  RESULTS
  Neutralization of IFN-gamma significantly attenuated concanavalin A-induced hepatic injury. However, neutralization of IL-17 failed to suppress the injury. Inactivation of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-alpha, IL-6 and IFN-gamma but not IL-17.
  
  
  CONCLUSIONS
  Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-alpha, IL-6 and IFN-gamma.
authors: Zhejiang University School of Medicine, Hangzhou 310003, China.
authors: Lin
authors: L
authors: Chen
authors: Xiao-Jun
authors: XJ
authors: Xie
authors: Yu-Fu
authors: YF
authors: Ye
authors: Lin
authors: L
authors: Zhou
authors: Hai-Yang
authors: HY
authors: Xie
authors: Qin-Fen
authors: QF
authors: Xie
authors: Jiong
authors: J
authors: Tian
authors: Shu-Sen
authors: SS
authors: Zheng
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D003208:Concanavalin A / Q000633:toxicity*; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D003208:Concanavalin A; D007371:Interferon-gamma; D005682:Gadolinium; C038958:gadolinium chloride