Abstract
In order to determine the effect of UV radiation on β-defensin 3 (BD3) expression in human skin, freshly-isolated UV-naïve skin was obtained from newborn male infants undergoing planned circumcision. Skin explants sustained ex vivo dermis side down on RPMI media were exposed to 0.5 kJ/m (2) UVB, and biopsies were taken from the explant through 72 hours after radiation. mRNA expression was measured by qRTPCR and normalized to TATA-binding protein. BD3 expression at each time point was compared with an untreated control taken at time 0 within each skin sample. Extensive variability in both the timing and magnitude of BD3 induction across individuals was noted and was not predicted by skin pigment phenotype, suggesting that BD3 induction was not influenced by epidermal melanization. However, a mock-irradiated time course demonstrated UV-independent BD3 mRNA increases across multiple donors which was not further augmented by treatment with UV radiation, suggesting that factors other than UV damage promoted increased BD3 expression in the skin explants. We conclude that BD3 expression is induced in a UV-independent manner in human skin explants processed and maintained in standard culture conditions, and that neonatal skin explants are an inappropriate model with which to study the effects of UV on BD3 induction in whole human skin.
Highlights
The melanocortin 1 receptor (MC1R) is a Gs-protein-coupled receptor expressed on melanocytes that regulates several key aspects of cutaneous UV responses
When bound by agonistic ligands, most notably α-melanocyte stimulating hormone[1], MC1R initiates a cascade of UV-protective events mediated by activation of adenylyl cyclase and generation of cAMP that result in melanin production and enhanced genome stability via enhancement of DNA repair[2]
It has become clear that β-defensin 3 (BD3), known for its role in innate antimicrobial immunity, binds and influences MC1R signaling as a neutral MC1R agonist that blunts α-melanocyte stimulating hormone (αMSH)-mediated MC1R activation as well as agouti signaling protein (ASIP)-mediated
Summary
Any reports and responses or comments on the Keywords beta-defensin , UV radiation , qRTPCR , mRNA article can be found at the end of the article. Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Wolf Horrell E and D'Orazio J. UV-independent induction of beta defensin 3 in neonatal human skin explants [version 2; peer review: 2 approved, 1 approved with reservations] F1000Research 2015, 3:288 TNFα in the skin biopsies that indicate UV-independent TNFα expression, consisting with the hypothesis that wounding responses may be relevant to these observations. TNFα expression correlated with beta defensin 3 levels. We include histology sections that suggest that skin explants remain viable in culture conditions through 24h
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
