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The use of tissue‐engineered skin to demonstrate the negative effect of CXCL5 on epidermal ultraviolet radiation‐induced cyclobutane pyrimidine dimer repair efficiency
Author(s) -
Dorr M.M.,
Guignard R.,
Auger F.A.,
Rochette P.J.
Publication year - 2021
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.19117
Subject(s) - pyrimidine dimer , cyclobutane , dimer , ultraviolet radiation , ultraviolet , photochemistry , pyrimidine , irradiation , chemistry , materials science , medicine , optoelectronics , biochemistry , organic chemistry , radiochemistry , dna repair , dna , physics , ring (chemistry) , nuclear physics
Summary Background Ultraviolet radiation ( UVR ) is responsible for keratinocyte cancers through the induction of mutagenic cyclobutane pyrimidine dimers ( CPD s). Many factors influence CPD repair in epidermal keratinocytes, and a better understanding of those factors might lead to prevention strategies against skin cancer. Objectives To evaluate the impact of dermal components on epidermal CPD repair efficiency and to investigate potential factors responsible for the dermal–epidermal crosstalk modulating UVR ‐induced DNA damage repair in keratinocytes. Methods A model of self‐assembled tissue‐engineered skin containing human primary keratinocytes and fibroblasts was used in this study. Results We showed that CPD repair in keratinocytes is positively influenced by the presence of a dermis. We investigated the secretome and found that the cytokine CXCL 5 is virtually absent from the culture medium of reconstructed skin, compared with media from fibroblasts and keratinocytes alone. By modulating CXCL 5 levels in culture media of keratinocytes, we have shown that CXCL 5 is an inhibitor of CPD repair. Conclusions This work outlines the impact of the secreted dermal components on epidermal UVR ‐induced DNA damage repair and sheds light on a novel role of CXCL 5 in CPD repair.