Pharmacological Inhibition of Gal-3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium-Induced Colitis

被引:30
作者
Markovic, Bojana Simovic [1 ]
Nikolic, Aleksandar [1 ]
Gazdic, Marina [1 ]
Nurkovic, Jasmin [2 ]
Djordjevic, Irena [1 ]
Arsenijevic, Nebojsa [1 ]
Stojkovic, Miodrag [1 ,3 ]
Lukic, Miodrag L. [1 ]
Volarevic, Vladislav [1 ]
机构
[1] Univ Kragujevac, Fac Med Sci, Ctr Mol Med & Stem Cell Res, 69 Svetozar Markovic St, Kragujevac 34000, Serbia
[2] State Univ Novi Pazar, Dept Biomed Sci, Stem Cell Lab, Nn Vuk Karadzic St, Novi Pazar 36300, Serbia
[3] Spebo Med, 16 Norvezanska St, Leskovac 16000, Serbia
关键词
DENDRITIC CELLS; TARGETED DISRUPTION; STROMAL CELLS; GALECTIN-3; MICE; INFLAMMATION; PROLIFERATION; DISEASE; MODELS; INJURY;
D O I
10.1155/2016/2640746
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
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.
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页数:12
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