Galectin-3 deficiency prevents concanavalin A-induced hepatitis in mice

• 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 Ainduced 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 Ainduced hepatitis and had a significantly lower number of activated lymphoid and dendritic cells (DCs) in the liver. The level of tumor necrosis factor alpha (TNFa), interferon gamma (IFN?), and interleukin (IL)-17 and -4 in the sera and the number of TNFa-, IFN?-, 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 IFN?- 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 Ainduced 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. (HEPATOLOGY 2012;55:19541964)

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

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