Publikationsserver der Universitätsbibliothek Marburg

Titel:Die Rolle von Cathelizidin und des Transkriptionsfaktors NF-kB bei Asthma und COPD
Autor:Klescz, Frank Friedhelm
Weitere Beteiligte: Bals, Robert (Prof. Dr. Dr.)
Veröffentlicht:2010
URI:https://archiv.ub.uni-marburg.de/diss/z2010/0245
DOI: https://doi.org/10.17192/z2010.0245
URN: urn:nbn:de:hebis:04-z2010-02455
DDC: Biowissenschaften, Biologie
Titel (trans.):The role of cathelicidine and the transcription factor NF-kB in the context of asthma and COPD
Publikationsdatum:2010-04-27
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Bronchialasthma, asthma, COPD, NF-kB, cathelicidine, Allergisches Asthma, Cathelizidin, NF-kB, Obstruktive Ventilationsstörung

Zusammenfassung:
Asthma und COPD sind zwei komplexe Lungenkrankheiten. Sowohl Asthma als auch COPD besitzen eine starke entzündliche Komponente, bei der jeweils verschiedene Teile des Immunsystems und der Lunge involviert sind. NF-κB ist ein wichtiger Transkriptionsfaktor, der die Aktivität vieler Gene des Immunsystems kontrolliert. Antimikrobielle Pepdide sind Effektormoleküle des angeborenen Immunsystems, die an Abwehr- und Entzündungsreaktionen des Wirtsorganismus beteiligt sind. Da Cathelizidine sowohl antimikrobielle als auch immunmodulatorische Eigenschaften besitzen, könnten sie sich auf die Pathogenese des Asthma und der COPD auswirken. Ziel dieser Arbeit war es, die Rolle des murinen Cathelicidins CRAMP und des Transkriptionsfaktors NF-κB in Asthma und COPD zu klären. Die Analyse der bronchoalveolaren Lavage (BAL), der in der Lunge enthaltenen Zytokine und des im Serum enthaltenen IgE zeigte, das Cathelizidin keine Rolle bei experimentell induziertem akuten Asthma spielt. Bei chronischem experimentellen Asthma hatte Cathelizidin einen komplexen Effekt, da CRAMP-/--Mäuse einen leicht erhöhten Gesamtzellgehalt und mehr Eosinophile in ihrer BAL als Wildtypmäuse (WT-Mäuse) aufwiesen. Allerdings war der Spiegel an Serum-IgE und TH2-Zytokinen in der Lunge bei CRAMP-/--Mäusen niedriger als bei WT-Mäusen. Bei kurzzeitiger Zigarettenrauchexposition wirkte CRAMP entzündungshemmend, da die BAL bei CRAMP-/--Mäusen mehr Zytokine als bei gleichbehandelten WT-Mäusen enthielt. Im chronischen COPD-Modell konnte ebenfalls eine entzündungshemmende Wirkung von CRAMP festgestellt werden, da bei CRAMP-/--Mäusen sowohl die Gesamtzellzahl in ihrer BAL als auch verschiedene Zytokinkonzentrationen im Serum und in der Lunge gegenüber gleichbehandelten WT-Mäusen erhöht waren. Bei akutem experimentellen Asthma konnte gezeigt werden, dass der p65-vermittelte NF-κB-Signalweg eine wichtige Rolle spielt. Eine ständige Aktivierung des p65-vermittelten NF-κB-Signalwegs in myeloischen Zellen führte zu einem neutrophilen Phänotyp und wirkte teilweise entzündungshemmend, wohingegen eine dauerhafte Hemmung des p65-vermittelten NF-κB-Signalwegs in myeloischen Zellen teilweise entzündungsfördernd wirkte. Im akuten Rauchexpositionsmodell konnte keine Beteiligung des myeloischen NF-κB-Signalwegs an den Reaktionen der untersuchten Tiere im Rahmen der untersuchten Parameter festgestellt werden. Im chronischen COPD-Modell jedoch konnte gezeigt werden, dass die Aktvierung von p65 in myeloischen Zellen entzündungshemmend wirkt. Die Ergebnisse dieser Arbeit zeigen, dass das murine Cathelizidin CRAMP neben seiner antimikrobiellen Wirkung auch immunmodulatorische Funktionen besitzt. CRAMP wirkt bei COPD entzündungshemmend, und im Asthmamodell wirkt CRAMP als proasthmatischer Faktor. Die NF-κB-Signalkaskade myeloischer Zellen wirkt teilweise entzündungshemmend und teilweise entzündungsfördernd. Bei experimenteller COPD wirkt sich aktives myeloisches NF-κB entzündungshemmend aus, bei experimentell induziertem Asthma hingegen teils entzündungsfördernd und entzündungshemmend. Cathelizidin und NF-κB greifen in die komplexe Genese entzündlicher Lungenerkrankungen ein.

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