Humanes Beta-Defensin 1: Aus der Defensive gelockt

Zusammenfassung

Der Darm eines erwachsenen Menschen enthält etwa ein Kilogramm kommensale Bakterien. Diese Mikroorganismen stellen eine potenzielle Bedrohung dar, sodass ein effizientes Abwehrsystem essenziell zur Verhinderung von bakterieller Translokation und Infektionen ist. Neben anderen Verteidigungsmechanismen produziert der Mensch antimikrobielle Peptide (AMPs) als körpereigene Antibiotika, die in der Lage sind, Mikroorganismen abzutöten. Die wichtigste Gruppe der humanen AMPs sind die Defensine. Unter diesen spielt das humane β-Defensin 1 (hBD-1) eine entscheidende Rolle, denn es wird konstitutiv von allen Epithelien produziert. Allerdings war die biologische Funktion des hBD-1 lange unklar, denn im Gegensatz zu anderen AMPs zeigte es in vitro kaum antibiotische Aktivität. Jedoch sind verschiedene Erkrankungen mit genetischen Polymorphismen im hBD-1-Gen assoziiert. Hier diskutieren wir, warum die wahre Aktivität von hBD-1 bislang übersehen wurde und wie hBD-1 durch chemische Reduktion aktiviert werden kann. Wir erörtern die biologische Bedeutung der Aktivierung und die Bedeutung für chronisch-entzündliche Darmerkrankungen.

Abstract

The human gut is colonised by about one kilogram of commensal bacteria. These microorganisms are a potential threat, thus an efficient defence system is crucial in preventing bacterial translocation and infection. Besides other mechanisms of protection humans produce antimicrobial peptides (AMPs) that are able to kill a broad range of microorganisms. The human beta-defensin 1 (hBD-1) plays a major role because it is produced constitutively by all human epithelia and some immune cells. In contrast to other AMPs, however, the biological function of hBD-1 has remained unclear since the antibiotic activity of hBD-1 in vitro was only marginal. But still, several diseases have been associated with genetic polymorphisms in the hBD-1 encoding gene. Herein we discuss why the biological role of hBD-1 has been overlooked and how hBD-1 can be activated by chemical reduction. We elaborate on the biological significance of this activation and its importance for inflammatory bowel disease.

Schlüsselwörter

Defensin - hBD-1 - kommensale Bakterien - chronisch entzündliche Darmerkrankung

Key words

defensin - hBD-1 - commensal bacteria - chronic inflammatory bowel disease

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