Chronic UV exposure decreases sun sensitivity by a tanning independent mechanism
Craig, Sarah ; Viros, Amaya
Craig, Sarah
Viros, Amaya
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Abstract
Keratinocytes protect themselves from UV-induced damage and death by signalling to melanocytes
to produce and transfer melanin to protect their nuclei from further UV damage.
The keratinocyte-melanocyte communication axis defines the tanning response, which is
integral to epidermal homeostasis. We studied the effects of occasional, moderate and
chronic UVA/UVB exposure on keratinocytes in vitro using immortalised human keratinocytes
in monoculture. We show that UV exposure led to UV signature 7 mutations with
predominant C>T nucleotide substitutions across the genome. We observed that keratinocytes
with any UV treatment history were better able to withstand further UV exposure,
showing decreased UV sensitivity, despite the absence of melanin transfer from melanocytes.
We explored our findings in vivo using immunocompetent wild type mice, and observed a
striking decrease in sunburn cells (apoptotic keratinocytes), TUNEL, p53 and TT-dimers 24
hours after UV exposure in skin that had a prior history of significant UV damage. This in vivo
response is independent of melanin protection, as mouse melanocytes are intradermal and do
not transfer melanin to epidermal keratinocytes. These data show that chronic UV confers
protection to further UV exposure independently of the tanning response. We are investigating
transcriptional and immune changes that may infer a mechanism.
Authors
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Craig S, Viros A. 518 Chronic UV exposure decreases sun sensitivity by a tanning independent mechanism. Journal of Investigative Dermatology. 2021;141(5).