Therapeutic potential of the classical pathway complement inhibitor analogue PRP-B0 in an acute inflammatory bowel disease model.Anžič, Andreja (Avtor) Oven, Irena (Mentor) Aran, M. Josep (Komentor) acute inflammatory bowel diseaseCrohn’s diseaseulcerative colitisPRP-B0therapeutic potentialclassical pathway complement inhibitorInflammatory bowel disease is a chronic disorder of the gastrointestinal tract that comprises two major conditions: Crohn’s disease and ulcerative colitis. The main focus of treating IBD so far was focused towards strategies which regulate the immune response. C4b-binding protein is plasma glycoprotein and a major soluble inhibitor of the classical and lectin pathways of complement activation. Our study describes a new mechanism of action in which an analogue of C4b-binding protein called PRP-B0 might affect activation of dendritic cells. We predicted that the dendritic cells treated with PRP-B0 would lower Th1 proinflammatory cytokines and increase IL-10, cytokine that inhibits Th1-immune response and, therefore, would improve intestinal damage. An experiment using C57BL/6 mice that lasted 9 days was made, where we induced a condition similar to ulcerative colitis using 2% dextran sodium sulfate at day 0. After that, animals were treated with either PRP-B0 or received a daily treatment with minocycline (reference treatment). We also had a control group, which was injected with Dulbecco's phosphate-buffered saline. After 9 days animals were sacrificed, and a disease activity index score was applied for each animal in order to evaluate the colon inflammatory status. The presence of multiple cytokines and chemokines in mouse serum samples were assessed using the Proteome profile array. Moreover, the presence of endotoxin in mice serum was evaluated. Afterwards an accurate quantification of chemokine CXCL13 in mouse serum was made through enzyme-linked immunosorbent assay. According to the results obtained, PRP-B0 could be a promising biological for inflammatory bowel disease treatment.[A. Anžič]20202020-01-24 07:45:03Magistrsko delo/naloga113678UDK: 606:616.34:577.27(043.2)VisID: 175591COBISS_ID: 18307331sl