title: Protective role of IL-33/ST2 axis in Con A-induced hepatitis.
abstract: OBJECTIVE
  We used Concanavalin A-induced liver injury to study the role of Interleukin 33 and its receptor ST2 in the induction of inflammatory pathology and hepatocellular damage.
  
  
  METHODS
  We tested susceptibility to Concanavalin A induced hepatitis in ST2 deficient and wild type BALB/c mice and analyzed the effects of single injection of Interleukin 33 as evaluated by liver enzyme test, quantitative histology, mononuclear cell infiltration, cytokine production, intracellular staining of immune cells, and markers of apoptosis in the liver.
  
  
  RESULTS
  ST2 deficient mice developed significantly more severe hepatitis and had significantly higher number of mononuclear cells in the liver, CD4+ and CD8+ T cells, NKp46+ and CD3+NKp46+ cells, and F4/80+ macrophages. The level of pro-inflammatory cytokines in the sera and number of TNF alpha, IFN gamma, and IL-17 producing cells was higher in ST2 deficient mice. In contrast, number of CD4+Foxp3+ cells was statistically higher in wild type mice. Additionally, treatment of wild type mice with single (1 μg) injection of Interleukin 33 led to attenuation of the liver injury and milder infiltration of mononuclear cells, increase in total number of liver CD4+Foxp3+ cells and IL-4 producing CD4+ T cells. Interleukin 33 also suppressed the activation of caspase 3, prevented the expression of BAX, and enhanced the expression of antiapoptotic Bcl-2 in the liver.
  
  
  CONCLUSIONS
  We concluded that Interleukin 33/ST2 axis downregulated Concanavalin A-induced liver injury and should be evaluated as potential target in fulminant hepatitis in humans.
authors.affiliation: Department of Microbiology and Immunology, Centre for Molecular Medicine and Stem Cell Research, Faculty of Medicine, University of Kragujevac, Serbia.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Volarevic
authors.forename: Marina
authors.initials: M
authors.lastname: Mitrovic
authors.forename: Marija
authors.initials: M
authors.lastname: Milovanovic
authors.forename: Ivanka
authors.initials: I
authors.lastname: Zelen
authors.forename: Ivana
authors.initials: I
authors.lastname: Nikolic
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Mitrovic
authors.forename: Nada
authors.initials: N
authors.lastname: Pejnovic
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Arsenijevic
authors.forename: Miodrag L
authors.initials: ML
authors.lastname: Lukic
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D003208:Concanavalin A / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000008:administration & dosage / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D003208:Concanavalin A