Dokument

Zusammenfassung:
Mit Hilfe sogenannter pattern recognition receptors kann das angeborene Immunsystem bakterielle Molekülmuster (pathogen associated molecular patterns) gramnegativer und grampositiver Bakterien erkennen und bestimmte Abwehrmechanismen einleiten. Von entscheidender Bedeutung sind dabei Toll-like Rezeptoren, die von verschiedensten Zelltypen, darunter auch Epithelzellen und Fibroblasten, exprimiert werden. Im Rahmen parodontaler Erkrankungen wird TLR9 eine wichtige Rolle bei der Erkennung doppelsträngiger bakterieller DNA periodontopathogener Keime zugesprochen, die als PAMP zu einer Produktion proinflammatorischer Zytokine und, bei verspäteter oder ausbleibender Therapie, zu einer chronisch progredienten Inflammation und Destruktion des Zahnhalteapparats führen kann. Um die immunologischen Effekte im Rahmen der Parodontitis zu untersuchen, wurde in der vorliegenden Arbeit eine in vitro-Kultur primärer humaner Gingiva-Fibroblasten (HGFs) mit unterschiedlichen TLR9-Liganden stimuliert, um eine Sekretion proinflammatorischer Zytokine auszulösen und mittels ELISA zu quantifizieren. Als Referenzsystem dienten hierbei neben TLR9-transfizierten HEK-293 Zellen auch humane PBMCs. Das Hauptziel dieser Arbeit sollte die Inhibition einer durch bDNA induzierten TLR9-Aktivierung in HGFs in vitro durch den Einsatz spezifischer suppressiver Oligodeoxynukleotide sein. Zusammenfassend zeigen die Ergebnisse, dass die verschiedenen verwendeten Zellsysteme unterschiedliche Stimulationsverhalten aufwiesen, die allesamt durch das inhibitorische Oligodeoxynukleotid G-ODN signifikant inhibiert werden konnten. Die Ergebnisse wurden in Zusammenhang mit mukosaler Immunität gestellt und der therapeutische Einsatz von G-ODN in bDNA-induzierter Parodontitis diskutiert.

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