Galectin-3 deficiency prevents concanavalin A-induced hepatitis in mice
(2012) In Hepatology 55(6). p.1954-1964- 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 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... (More)
- 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) (Less)
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https://lup.lub.lu.se/record/2906506
- author
- Volarevic, Vladislav ; Milovanovic, Marija ; Ljujic, Biljana ; Pejnovic, Nada ; Arsenijevic, Nebojsa ; Nilsson, Ulf LU ; Leffler, Hakon and Lukic, Miodrag L.
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Hepatology
- volume
- 55
- issue
- 6
- pages
- 1954 - 1964
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000304530200032
- scopus:84861574827
- pmid:22213244
- ISSN
- 1527-3350
- DOI
- 10.1002/hep.25542
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240), Division of Microbiology, Immunology and Glycobiology - MIG (013025200)
- id
- b5da7c3c-ffb1-4b07-8e43-0c1b1fc2f0e0 (old id 2906506)
- date added to LUP
- 2016-04-01 13:07:24
- date last changed
- 2022-02-26 19:28:33
@article{b5da7c3c-ffb1-4b07-8e43-0c1b1fc2f0e0, 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 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)}}, author = {{Volarevic, Vladislav and Milovanovic, Marija and Ljujic, Biljana and Pejnovic, Nada and Arsenijevic, Nebojsa and Nilsson, Ulf and Leffler, Hakon and Lukic, Miodrag L.}}, issn = {{1527-3350}}, language = {{eng}}, number = {{6}}, pages = {{1954--1964}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Hepatology}}, title = {{Galectin-3 deficiency prevents concanavalin A-induced hepatitis in mice}}, url = {{http://dx.doi.org/10.1002/hep.25542}}, doi = {{10.1002/hep.25542}}, volume = {{55}}, year = {{2012}}, }