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Title: Protective role of IL-33/ST2 axis in Con A-induced hepatitis
Authors: Volarevic, Vladislav
Mitrovic M.
Milovanovic, Marija
Zelen I.
Nikolic, Ivana
Mitrović I.
Pejnović, Nada
Arsenijevic, Nebojsa
Lukic, Miodrag
Issue Date: 2012
Abstract: Background & Aims: 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. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Type: article
DOI: 10.1016/j.jhep.2011.03.022
ISSN: 0168-8278
SCOPUS: 2-s2.0-83555160892
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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