title: Pharmacological Inhibition of Gal-3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium-Induced Colitis.
abstract: Transplantation of mesenchymal stem cells (MSCs) reduces the severity of dextran sulphate sodium- (DSS-) induced colitis. MSCs are able to secrete Galectin-3 (Gal-3), a protein known to affect proliferation, adhesion, and migration of immune cells. We investigate whether newly synthetized inhibitor of Gal-3 (Davanat) will affect production of Gal-3 in MSCs and enhance their potential to attenuate DSS-induced colitis. Pharmacological inhibition of Gal-3 in MSCs enhances their capacity to promote alternative activation of peritoneal macrophages in vitro and in vivo. Injection of MSCs cultured in the presence of Davanat increased concentration of IL-10 in sera of DSS-treated animals and markedly enhanced presence of alternatively activated and IL-10 producing macrophages in the colons of DSS-treated mice. Pharmacological inhibition of Gal-3 in MSCs significantly attenuates concentration of Gal-3 in sera of DSS-treated animals, indicating that MSCs produce Gal-3 in this disease. In conclusion, our findings indicate that Davanat could be used for improvement of MSC-mediated polarization towards immunosuppressive M2 phenotype of macrophages.
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Simovic Markovic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Nikolic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Gazdic
authors.affiliation: Stem Cell Laboratory, Department of Biomedical Sciences, State University of Novi Pazar, Nn Vuk Karadzic Street, 36300 Novi Pazar, Serbia.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Nurkovic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Djordjevic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Arsenijevic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia; Spebo Medical, 16 Norvezanska Street, 16000 Leskovac, Serbia.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Stojkovic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
authors.forename: Miodrag L
authors.initials: ML
authors.lastname: Lukic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Volarevic