title: Innate immune reactivity of the ileum-liver axis in nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Over-proliferation and bacterial translocation of Gram-negative bacilli within the intestinal flora, and increased portal venous levels of endotoxins, are involved in nonalcoholic steatohepatitis (NASH).
  
  
  OBJECTIVE
  To evaluate the innate immune response in the small intestine and liver using the rat NASH model.
  
  
  METHODS
  We produced the NASH model by administering a choline-deficient amino acid-defined diet to F344 rats. We analyzed the serum and liver tissue to assess the effects of innate immune reactivity in this NASH model.
  
  
  RESULTS
  Significant increases were detected in serum ALT levels and in the portal venous serum and whole-liver levels of TNF-α and IFN-γ in the NASH group. Strong Sirius red staining and TNF-α immune staining were seen in the NASH group, and real-time PCR revealed significantly increased expression of TNF-α and TLR4 mRNA in the NASH group. Higher TNF-α levels were detected in the Kupffer cells isolated culture supernatant in the NASH group than in the control group. Immune staining of the ileal tissue specimens resulted in greater staining of TNF-α, TLR4, and macrophage/dendritic cells, mainly in the submucosa, in the NASH group than in the control group.
  
  
  CONCLUSIONS
  In the small intestine and liver of the rat NASH model, the possibility that enhancement of the innate immune response, mediated by the TLR4 signal, led to increased production of TNF-α was suggested. This interaction between the small intestine and liver may be involved in the onset and progression of NASH.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. tat-tyan@xa2.so-net.ne.jp
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Tsujimoto
authors.forename: Hideto
authors.initials: H
authors.lastname: Kawaratani
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kitazawa
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D018988:Bacterial Translocation; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006090:Gram-Negative Bacteria / Q000502:physiology*; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D007113:Immunity, Innate; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4; D048069:Tumor Necrosis Factors; D000410:Alanine Transaminase