Human beta-defensin-3 promotes wound healing in infected diabetic wounds

Autor: Hans U. Steinau, Baraa Zuhaili, Magdalena Fossum, Till Koehler, Andrew B. Onderdonk, Feng Yao, Tobias Hirsch, Lars Steinstraesser, Malte Spielmann, Marie Metzig, Elof Eriksson
Rok vydání: 2009
Předmět:
Zdroj: The Journal of Gene Medicine. 11:220-228
ISSN: 1521-2254
1099-498X
Popis: Background Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds. Methods Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation. Results hBD-3-treated wounds showed a total bacterial load of 2.1 × 108 colony-forming units (CFU)/g tissue, versus 1.3 × 109 CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 ± 15% wound closure for hBD-3 expressing wounds and 50 ± 16% for controls (p < 0.01). hBD-3 expression was in the range 15–20 ng/ml of wound fluid during day 1–4. The lower dose of 2 × 109 Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3. Conclusions In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta-defensin-3 may play a major role in diabetic wound healing and wound infections. Copyright © 2008 John Wiley & Sons, Ltd.
Databáze: OpenAIRE
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