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Allerdings ist bisher unklar, welche Bedeutung BPI für Chronisch-entzündliche-Darmerkrankungen (CED) hat. Im Rahmen dieser Arbeit konnte erstmals gezeigt werden, dass BPI eine wichtige Funktion bei der DSS-induzierten Kolitis einnimmt. Dabei konnte in Wildtyp (WT) - Mäusen eine gesteigerte BPI-Expression während einer DSS-induzierten Kolitis nachgewiesen werden. Beim Vergleich der Phänotypen von WT- und BPI defizienten (BPI-/-) - Mäusen zeigten sich deutliche Unterschiede im Krankheitsverlauf. Die Defizienz von BPI führte zu einer gesteigerten Suzseptibilität in Mäusen nach DSSGabe. Nähere Untersuchungen dazu zeigten, dass BPI-/- - Mäuse mit einer stärkeren Immunantwort reagieren. Diese ist durch eine gesteigerte Zytokinfreisetzung von IL-1ß und eine signifikant erhöhte Anzahl von Entzündungszellen im Darm gekennzeichnet. Bei den Entzündungszellen im Darm handelt es sich um T- und BZellen, Makrophagen und neutrophile Granulozyten. Erste mechanistische Analysen zeigten, dass BPI weder Einfluss auf intrinsische zytoprotektive Eigenschaften des Epithels hat, noch einen direkten Einfluss auf den IL17C Signalweg nimmt. IL-17C wird eine entscheidende Funktion bei der mukosalen Immunabwehr zugeschrieben. Auch die Analysen zur Zusammensetzung der Mikroflora im Darm von WT- als auch BPI-/- - Mäusen mittels quantitativer PCR lieferten keine signifikanten Unterschiede zwischen den Genotypen. BPI scheint demzufolge keinen direkten Einfluss auf die Zusammensetzung der untersuchten Mikrobiota zu haben, was jedoch durch weitere detaillierte Analysen der Bakterienarten klarifiziert werden sollte. Stromiedel, Maria Stromiedel Maria https://doi.org/10.17192/z2014.0441 urn:nbn:de:hebis:04-z2014-04411 doctoralThesis Activation and function of Bactericidal / Permeability - Increasing Protein (BPI) in inflammatory bowel disease https://archiv.ub.uni-marburg.de/diss/z2014/0441/cover.png The Lipopolysaccharid binding and neutralizing antimicrobial protein bactericidal / permeability - increasing protein (BPI) plays an important role in different diseases like for example cystic fibrosis. However, its role during inflammatory bowel disease is not clear. With this work we provided evidence that BPI determines the susceptibility of mice during DSS-induced colitis. The administration of DSS led to an increased expression of BPI-mRNA in the gut of wildtype mice (WT). Accordingly BPI-deficient (BPI-/-) mice developed a severe colitis after DSS treatment whereas WT mice were only mildly effected. Detailed analysis demonstrated that BPI-/- mice displayed a stronger immune response characterized by an enhanced cytokine secretion and a significant increased number of inflammatory cells in the effected gut. This was signified by a heightened IL-1ß production from the intestine as well as an enhanced number of macrophages, neutrophilic granulocytes, T-and B- cells in the inflamed gut of BPI-/- mice. First mechanistic investigations showed that BPI neither has an influence on the intrinsic cytoprotective properties of the gut epithelium nor does it control the IL-17C signaling pathway. IL-17C is thought to be decisive for the mucosal immune defense. Additionally, the analysis of the composition of the microbiota by quantiative PCR did not reveal any significant differences between the two genotypes analyzed. Therefore, BPI seems to have not a strong impact on the composition of the microbiota but this has to be clarified in future analysis in more details. Medizin Philipps-Universität Marburg application/pdf Inflammatory Bowel Disease 2014 Medizin German BPI 2014-05-26 2014-06-05 monograph 2014-06-05 ppn:340950145 Publikationsserver der Universitätsbibliothek Marburg Universitätsbibliothek Marburg