Expression of human beta-defensin-1 promotes differentiation of keratinocytes

Epithelial cells have been shown to express the antibiotic peptides human b eta -defensins-1 and 2. While beta -defensin-2 is known to be up-regulated by bacterial factors and proinflammatory mediators, the expression of beta -defensin-1 does not appear to be affected by these mediators. To determine the regulation and function of beta -defensin-1 we analyzed its expression upon stimulation of inflammatory mediators in vitro and ex vivo. In immort alized human cell lines (HaCaT) and nasal polyps beta -defensin-1 was not i nduced upon incubation with bacteria or proinflammatory mediators, suggesti ng that the inertness of beta -defensin-1 expression levels is not the resu lt of the shortcoming of HaCaT cells. As proliferation and regeneration pla y an important role at sites of inflammation, we examined the expression le vel of beta -defensin-1 in relation to the differentiation and proliferatio n of HaCaT cells. beta -defensin-1 mRNA levels remained low during prolifer ation but were highly induced upon differentiation. In contrast, beta -defe nsin-2 expression was unaffected under these conditions. To examine the fun ction of beta -defensin-1 in cellular proliferation and differentiation pro cesses beta -defensin-1 was overexpressed in keratinocytes. Protein express ion analysis of the differentiation marker keratin 10 revealed that its exp ression is highly induced in the presence of increased concentrations of be ta -defensin-1. Hence our data indicate that high expression of beta -defen sin-1 promotes cell differentiation processes of keratinocytes.