Interactions between Ultraviolet B (UVB) Radiation and Circadian Clock in the Skin

Veera Nikkola

    Research output: Book/ReportDoctoral thesisCollection of Articles


    In everyday life, ultraviolet (UV) radiation from the sun is a significant carcinogen. It induces deoxyribonucleic acid (DNA) mutations and, at the same time, is immunosuppressive. From the whole solar UV radiation spectrum, the wavelengths of UVB are the most biologically active part.

    There are indications that the timing of UVB exposure may affect sensitivity to sunburn, but these findings have not been confirmed in human studies. However, almost all functions of the human skin are rhythmic in a circadian (approximately a day of 24 hours) manner, and most skin cell types have their own intrinsic circadian clock. Similar to the central circadian clock in the brain, the human skin expresses clock proteins, e.g., cryptochromes which are essential to circadian function, and melatonin, which is well known for its ability to influence human chronobiology. So far, little is known about the link between skin clock proteins, melatonin, and erythema.

    In the skin, UVB induced erythema is a consequence of vasodilatation after DNA damage. In this thesis, we aimed to investigate, if there were connections between skin erythema and the circadian clock.
    In order to investigate the impact of the hour of the day on UVB induced erythema, we performed photosensitivity testing of the skin of 19 healthy volunteers twice, first in the morning and second in the evening. Using immunohistochemistry we also analysed skin biopsies taken at a different hour of the day, the expression of the core clock proteins. Erythema was found to be more pronounced after evening irradiations than after morning irradiations. Cryptochrome-2 (CRY2) was identified as a possible protecting factor.

    The effect of UVB irradiation on circadian time in the skin was studied by performing mRNA expression analyses on skin samples obtained from 12 healthy volunteers. We compared expression of clock proteins in non-irradiated and UVB irradiated skin samples and in corresponding samples of subcutaneous adipose tissue. UVB exposures seemed to modify the expression of CRY2 in epidermal and dermal skin, and that of Cryptochrome-1 (CRY1) and Circadian-associated transcriptional repressor (CIART) in subcutaneous adipose tissue. Irradiation also altered the CRY1/CRY2 ratio.

    In a further study, 39 healthy volunteers were analyzed using immunohistochemistry for the presence of melatonin in the non-UVB exposed buttocks skin at different times of the day. The photosensitivity testing was performed on the skin of all our volunteers. We discovered melatonin content of the non-irradiated skin to vary diurnally. However melatonin expression in the skin detected by immunohistochemistry did not correlate with the circadian change in erythema sensitivity.

    In conclusion, the hour of the day of UVB irradiation seems to influence the erythema formation in healthy human skin. The connection is also reverse, because UVB irradiation changes the mRNA expression of clock driving proteins. It is possible that UVB serves as a cue for circadian time entrainment through the skin. Even though the melatonin content of the skin varies diurnally this does not appear to be the reason why UVB induces more erythema in the evening than in the morning. Understanding factors influencing erythema sensitivity of the skin and its interactions with the circadian clock could promote the development of skin cancer prevention strategies as well as dermatological treatments. An extensive understanding of circadian clock entrainment is an important part of overall human health.
    Original languageEnglish
    Place of PublicationTampere
    PublisherTampere University
    ISBN (Electronic)978-952-03-1874-1
    ISBN (Print)978-952-03-1873-4
    Publication statusPublished - 2021
    Publication typeG5 Doctoral dissertation (articles)

    Publication series

    NameTampere University Dissertations - Tampereen yliopiston väitöskirjat
    ISSN (Print)2489-9860
    ISSN (Electronic)2490-0028


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