title: Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice.
abstract: BACKGROUND
  The role of Kupffer cell interleukin (IL)-1 in non-alcoholic steatohepatitis development remains unclear.
  
  
  OBJECTIVE
  To evaluate the role of Kupffer cell IL-1α, IL-1β or IL-1 receptor type-1 (IL-1R1) in steatohepatitis.
  
  
  METHODS
  C57BL/6 mice were irradiated and transplanted with bone marrow-derived cells from WT, IL-1α-/-, IL-1β-/- or IL-1R1-/- mice combined with Kupffer cell ablation with Gadolinium Chloride, and fed atherogenic diet. Plasma and liver triglycerides and cholesterol, serum alanine aminotransferase (ALT), liver histology and expression levels of inflammatory genes were assessed.
  
  
  RESULTS
  The ablation and replacement of Kupffer cells with bone marrow-derived cells was confirmed. The atherogenic diet elevated plasma and liver cholesterol, reduced plasma and liver triglycerides and increased serum ALT levels in all groups. Steatosis and steatohepatitis were induced, but without liver fibrosis. A reduction in the severity of portal inflammation was observed only in mice with Kupffer cell deficiency of IL-1α. Accordingly, liver mRNA levels of inflammatory genes encoding for IL-1α, IL-1β, TNFα, SAA1 and IL-6 were significantly lower in mice with Kupffer cell deficiency of IL-1α compared to WT mice.
  
  
  CONCLUSIONS
  Selective deficiency of IL-1α in Kupffer cells reduces liver inflammation and expression of inflammatory cytokines, which may implicate Kupffer cell-derived IL-1α in steatohepatitis development.
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Sarita
authors.initials: S
authors.lastname: Olteanu
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Kandel-Kfir
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Aviv
authors.initials: A
authors.lastname: Shaish
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Almog
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Shemesh
authors.affiliation: Pathology Department, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: Department of Microbiology and Immunology, Ben Gurion University, Beer Sheva, Israel.
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel. Electronic address: yehuda.kamari@sheba.health.gov.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Kamari
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D004036:Diet, Atherogenic; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006505:Hepatitis / Q000097:blood* / Q000235:genetics / Q000473:pathology; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000172:deficiency* / Q000235:genetics; D053583:Interleukin-1beta / Q000172:deficiency / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011168:Portal System; D012333:RNA, Messenger / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014657:Vasculitis / Q000378:metabolism
chemical_list: C508590:IL1R1 protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D053573:Receptors, Interleukin-1 Type I; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D000410:Alanine Transaminase
keywords: Cytokine; Fatty liver; IL-1; Inflammation; Kupffer cells; NASH