Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/10578
Title: Galectin-3 deficiency prevents concanavalin A-induced hepatitis in mice
Authors: Volarevic, Vladislav
Milovanovic, Marija
Ljujic, Biljana
Pejnović, Nada
Arsenijevic, Nebojsa
Nilsson U.
Leffler, Hakon
Lukic, Miodrag
Issue Date: 2012
Abstract: We used concanavalin A (Con A)-induced liver injury to study the role of galectin-3 (Gal-3) in the induction of inflammatory pathology and hepatocellular damage. We tested susceptibility to Con A-induced hepatitis in galectin-3-deficient (Gal-3 -/-) mice and analyzed the effects of pretreatment with a selective inhibitor of Gal-3 (TD139) in wild-type (WT) C57BL/6 mice, as evaluated by a liver enzyme test, quantitative histology, mononuclear cell (MNC) infiltration, cytokine production, intracellular staining of immune cells, and percentage of apoptotic MNCs in the liver. Gal-3 -/- mice were less sensitive to Con A-induced hepatitis and had a significantly lower number of activated lymphoid and dendritic cells (DCs) in the liver. The level of tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL)-17 and -4 in the sera and the number of TNFα-, IFNγ-, and IL-17- and -4-producing cluster of differentiation (CD)4 + cells as well as IL-12-producing CD11c + DCs were lower, whereas the number of IL-10-producing CD4 + T cells and F4/80 + macrophages were significantly higher in livers of Gal-3 -/- mice. Significantly higher percentages of late apoptotic Annexin V + propidium-idodide + liver-infiltrating MNCs and splenocytes were observed in Gal-3 -/- mice, compared to WT mice. Pretreatment of WT C57BL/6 mice with TD139 led to the attenuation of liver injury and milder infiltration of IFNγ- and IL-17- and -4-producing CD4 + T cells, as well as an increase in the total number of IL-10-producing CD4 + T cells and F4/80 + CD206 + alternatively activated macrophages and prevented the apoptosis of liver-infiltrating MNCs. Conclusions: Gal-3 plays an important proinflammatory role in Con A-induced hepatitis by promoting the activation of T lymphocytes and natural killer T cells, maturation of DCs, secretion of proinflammatory cytokines, down-regulation of M2 macrophage polarization, and apoptosis of MNCs in the liver. © 2012 American Association for the Study of Liver Diseases.
URI: https://scidar.kg.ac.rs/handle/123456789/10578
Type: article
DOI: 10.1002/hep.25542
ISSN: 0270-9139
SCOPUS: 2-s2.0-84861574827
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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