Die Aktivierung und Funktion von Bactericidal / Permeability - Increasing Protein (BPI) bei entzündlichen Darmprozessen

Das Antimikrobielle Protein (AMP) Bactericidal / Permeability - Increasing Protein (BPI), welches in der Lage ist, Lipopolysaccharide (LPS) effektiv zu binden und damit zu neutralisieren, spielt bei Erkrankungen wie z.B cystischer Fibrose eine entscheidende Rolle. Allerdings ist bisher unklar, we...

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Bibliographic Details
Main Author: Stromiedel, Maria
Contributors: Schnare, Markus (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2014
Medizin
Subjects:
BPI
Online Access:PDF Full Text
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Table of Contents: 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.