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Molecular aspects of UVB-induced immunosuppression
J Garssen1, R J Vandebriel, H van Loveren
1Laboratory for Pathology and Immunobiology, National Institute of Public health and the Environment, Bilthoven, The Netherlands.
Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement
|January 1, 1997
Summary
Ultraviolet (UV) light impairs immune resistance by altering skin photoreceptors like urocanic acid and DNA. DNA damage, specifically cyclobutyl pyrimidine dimers, plays a key role in UV-induced immunosuppression.
Area of Science:
- Immunology
- Photobiology
- Dermatology
Background:
- Ultraviolet (UV) radiation impacts immune function both locally and systemically.
- UVB absorption by skin chromophores initiates signals leading to altered immune responses.
- These alterations involve changes in cytokine profiles, growth factors, and costimulatory signals.
Purpose of the Study:
- To investigate the photoreceptors responsible for UV-induced immunosuppression.
- To elucidate the mechanisms of UV-induced immune alterations, focusing on DNA damage and gene expression.
- To explore the roles of urocanic acid (UCA), DNA photoproducts, and signal transduction pathways.
Main Methods:
- Examined the role of urocanic acid (UCA) isomerization from trans- to cis-isomer.
- Investigated DNA as a photoreceptor, analyzing UV-induced DNA alterations and photoproduct formation.
- Utilized mice models with and without DNA repair enzymes (T4 endonuclease) and DNA repair deficiencies to assess UV effects.
- Monitored gene expression changes and the involvement of specific cytokines (IL-10, TNF-alpha) and transcription factors (NF-kappa B, p91).
Main Results:
- Cis-urocanic acid (UCA) exhibits immunosuppressive properties.
- UV-induced DNA damage, particularly cyclobutyl pyrimidine dimers, is linked to immune suppression.
- Efficient removal of UVB-induced dimers using T4 endonuclease prevented immunosuppression in mice.
- Altered gene expression, potentially mediated by DNA damage, plays a pivotal role in UVB-induced immunosuppression.
- Signal transduction pathways and transcription factors are implicated in UV immunomodulation.
Conclusions:
- Both urocanic acid (UCA) and DNA act as key photoreceptors in UV-induced immunosuppression.
- UV-induced DNA damage and subsequent altered gene expression are critical mechanisms underlying immune suppression.
- Further research is needed to fully understand the complex signaling pathways involved in UV immunomodulation.