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The role of galectin 3 in acute colitis
Serbia (IFMSA-Serbia) - University of Kragujevac, Kragujevac
Center for Molecular Medicine and Stem Cells Research
Professor MD Vladislav Volarevi
Type of Research Project
- Basic science
What is the background of the project?
Gal-3 has been studied in the inflammatory diseases and tumors, but the exact role of Gal-3 in the pathogenesis of inflammatory bowel disease was not analyzed. The role of Gal-3 in theresponse to infection is studied and we have demonstrated its role in severalinflammatory diseases. Gal-3 has an important pro-inflammatory role in acutehepatitis by promoting the activation of T lymphocytes and Natural Killers T- lymphocytes cells, maturation of dendritic cells, secretion of proinflammatory cytokines, down-regulation of M2 macrophagepolarization, and apoptosis of mononuclear cells in the liver. Gal-3 is also involved inimmune-mediated β-cell damage and is required for pathogenesis of type 1 diabetesby promoting the expression of IFN-gamma, TNF-alpha, IL-17 and Inducible nitricoxide synthase in immune and accessory effectorcells. Gal-3 plays animportant disease-exacerbating role in Experimental autoimmune encephalomyelitis through its multifunctional roles inpreventing cell apoptosis and increasing IL-17 and IFN-gamma synthesis, butdecreasing IL-10 production.Genetic deletion of Gal-3 attenuates metastasis ofmurine melanoma by modulating tumor adhesion and activity of Natural Killers cells. Thus,evidence is accumulative that Gal-3 play an important role in infections, autoimmuneand immunometabolic diseases and its role in inflammatory bowel disease remain to be established.
What is the aim of the project?
The main aim of this project is to evaluate possible cellular and molecular targets of Gal-3 in the pathology of acute colitis.
What techniques and methods are used?
Animals: In this project, we will use 6-8 week old wild type (WT) C57BL/6 and galectin-3 knockout (galectin-3- /-) mice. Induction of acute colitis Dextran Sulphate Sodium (5%, molecular weight 40kDa; TdB Consultancy, Uppsala, Sweden) will be dissolved in water and given to mice in place of normal drinking water in 50 mL conical tubes. Assessment of the severity of colitis: Clinical and histological features of Dextran Sulphate Sodiumcolitis reflect those seen in human. Clinical features of Dextran Sulphate Sodium colitis induced in wild type and Gal-3- /- mice. Histological features of Dextran Sulphate Sodium colitis induced in wild type and Gal-3- /- mice. Establishing the difference in clinical and histological features of Dextran Sulphate Sodium -treated WT and Gal-3- /- mice. Testing the effect of genetic deletion of Gal-3 on the cytokine profile of Dextran Sulphate Sodium treated mice. The expression of inflammatory mediators in colonic tissue The expression of inflammatory mediators TNF-α, IL-1b, IL-6, IL-10, all involved in the pathogenesis of acute colitis, will be determined by Polymeraze Chain Reaction (PCR). The serum level of inflammatory mediators: The level of above mentioned cytokines will be measured in serum of Dextran Sulphate Sodium treated animals by using Enzyme-linked immunosorbent assay (ELISA) sets. Establishing the difference in cytokine profile of Dextran Sulphate Sodium - treated wild type and Gal-3- /- mice. Testing the role of Gal-3 in polarization and function of macrophages during the progression of Dextran Sulphate Sodium -induced colitis Isolation of macrophages from the colonic tissue of Dextran Sulphate Sodium treated wild type and Gal-3/- mice Phenotype and function of macrophages infiltrated in colons of Dextran Sulphate Sodium -treated wild type and Gal-3/- mice
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student is expected to learn techniques ofPolymeraze Chain Reaction which will be used fordetermination of expression of inflammatory mediators TNF-α, IL-1b, IL-6, IL-10, allinvolved in the pathogenesis of acute colitis, Enzyme-linked immunosorbent assaytests which will be used fordetermination of concentracion above mentionted cytokines in serum and FlowCytometry. All laboratory work will be done under supervision, and interpretation ofresults after lab work will be done by his/her own.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
We will provide the material for preliminary reading and lecture about the project and the metodology applied in project.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student’s name will be mentioned in a future publication - No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No skill are required
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system
- Radosavljevic G; Volarevic V; Jovanovic I; Milovanovic M; Pejnovic N; Arsenijevic N; Hsu DK; Lukic ML. The roles of Galectin-3 in autoimmunity and tumor progression. Immunol Res. 2012;52:100-110
- Volarevic V and Lukic ML. Autoimmune Disorders in Galectin-3 Deficient Mice; book chapter in Galectins and Disease implications in Targeted therapeutics edited by Klyosov A and Traber P. Chapter 21: pp 359?376. Chapter DOI: 10.1021/bk-20121115.ch021.
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