UV-independent induction of beta defensin 3 in neonatal human skin explants

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.

Does blue light restore human epidermal barrier function via activation of Opsin during cutaneous wound healing?

“…While all biopsies were taken from the same anatomical region of women of a similar age, biological variability, including hormonal fluctuations between different donors may explain the variability in wound closure . Donor variability has been previously reported in skin ex vivo cultures, which may be attributed to different inflammatory responses induced by tissue removal or different circadian rhythms as a consequence of the different environmental cues that individual donors have been exposed to (e.g. food intake, shift work, stress, smoking etc.…”

Melanocortin 1 Receptor: Structure, Function, and Regulation

“…UVB radiation, which induces POMC gene expression both in vivo and in vitro , has variable effects on βD3 induction, depending upon the experimental model. In vivo exposure of adult skin to UVB radiation led to increases in βD3 gene and protein expression ( Glaser et al, 2009 ), however, UV exposure of ex vivo neonatal skin explants did not induce βD3 expression suggesting that βD3 up-regulation following UVB exposure may require recruitment of additional cell types, potentially cytokine-producing immune cells, to the skin ( Wolf Horrell and D’Orazio, 2014 ).…”

Changes in antioxidant, inflammatory and metabolic markers during 1 week cultivation of human skin explants

“…HSE seems to be an excellent alternative for dermatological studies, as HSE maintains the 3D structure and contains most of the cell types present in the native skin, mainly keratinocytes at each stage of differentiation, melanocytes, dermal fibroblasts and Langerhans cells, and components of the ECM. Reports suggest a wide range of uses of HSE,e.g., the evaluation of radiation‐induced damage and protection (Arad, Konnikov, Goukassian, & Gilchrest, ; Davenport, Morris, Motazed, & Chu, ; Wolf Horrell & D’Orazio, ), skin wound healing (Harris, Bainbridge, Jordan, & Sharpe, ; Helbig, Mobius, Simon, & Paasch, ), contact dermatitis (Lehé et al, , Pistoor et al, ) or skin irritants (Jacobs, Lehé, Cammans, Das, & Elliott, ). However, the use of HSE has its limitations, such as a usability period due to irreversible changes—mainly basal layer degeneration, reduction of dermal papillae and subsequent separation of the dermis and epidermis (Kataranovski & Karadaglić, ; Lebonvallet et al, ).…”