Expression of human beta-defensin-1 promotes differentiation of keratinocytes.
Epithelial cells have been shown to express the antibiotic peptides human beta-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 immortalized human cell lines (HaCaT) and nasal polyps beta-defensin-1 was not induced upon incubation with bacteria or proinflammatory mediators, suggesting that the inertness of beta-defensin-1 expression levels is not the result of the shortcoming of HaCaT cells. As proliferation and regeneration play an important role at sites of inflammation, we examined the expression level of beta-defensin-1 in relation to the differentiation and proliferation of HaCaT cells. beta-defensin-1 mRNA levels remained low during proliferation but were highly induced upon differentiation. In contrast, beta-defensin-2 expression was unaffected under these conditions. To examine the function of beta-defensin-1 in cellular proliferation and differentiation processes beta-defensin-1 was overexpressed in keratinocytes. Protein expression analysis of the differentiation marker keratin 10 revealed that its expression is highly induced in the presence of increased concentrations of beta-defensin-1. Hence our data indicate that high expression of beta-defensin-1 promotes cell differentiation processes of keratinocytes.
Frye
M
M
Institute of Anthropology and Human Genetics, Johann Wolfgang Goethe-University, Frankfurt, Germany. M.Frye@em.uni-frankfurt.de
Bargon
J
J
Gropp
R
R
D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053550:Keratin-10; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism* / Q000382:microbiology; D007633:Keratins / Q000032:analysis / Q000235:genetics; D009298:Nasal Polyps / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000502:physiology; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
C406407:DEFB1 protein, human; C507493:KRT10 protein, human; D012333:RNA, Messenger; D023083:beta-Defensins; D053550:Keratin-10; D007633:Keratins