Further studies which precise and determine the molecular mechanism involved in the regulation of TH development and drug therapy in order to design therapeutic options that become applicable to improve the prognostic in these patients. Disclosures: The following people have nothing to disclose: Jorge A. López-Velázquez, Varenka J. Barbero-Becerra,

Vicente Sánchez- Valle, Ylse Gutiérrez-Grobe, Norberto C. Chavez-Tapia, José M. Ramírez-Jaramillo, Fredy Chablé-Montero, Misael N. Uribe-Esquivel, Nahum Méndez-Sanchéz “
“We used concanavalin A (Con A)-induced liver injury to study the role of galectin-3 (Gal-3) in the induction of inflammatory GSI-IX 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, JQ1 manufacturer 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 MCE 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. (HEPATOLOGY 2012;55:1954–1964) Concanavalin A (Con A)-induced liver injury is a well-established murine model of T-cell-mediated hepatitis. Intravenous (IV) injection of Con A induces acute liver injury and systemic immune activation in mice that resembles the pathology of immune-mediated hepatitis in humans.1 Activated T cells have a critical role in Con A–induced liver damage.