Document Detail


Molecular aspects of UVB-induced immunosuppression.
MedLine Citation:
PMID:  9079198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ultraviolet light can affect the immune system locally as well as systemically leading to an impaired resistance to neoplastic cells and/or infections. Prior to the biological effect, UVB must be absorbed by a chromophore in the skin where it will give a signal that can lead to an altered immune response in the skin or elsewhere. These altered immune responses may be constituted by alteration in among others: cytokine profile, growth factors and costimulatory signals. Several hypotheses about the identity of the photoreceptor have been put forward. One photoreceptor in the skin is urocanic acid (UCA), that can isomerize from the trans- to the cis-isomer. The cis-isomer has immunosuppressive properties. Another photoreceptor is DNA that also efficiently absorbs UV wavelengths. After absorption the structure of the DNA molecule is altered. This alteration might lead to gene activation responsible for the immunotoxic outcome (altered gene expression). It has been demonstrated that the formation of DNA photoproducts by UV light is associated with the activation of many genes. Several studies indicate that UV-induced DNA damage, in the form of cyclobutyl pyrimidine dimers plays a role in UV-induced suppression of the immune system locally as well as systemically. In mice that were injected with liposomes containing the excision repair enzyme T4 endonuclease UVB-induced dimers were removed more efficiently as compared to control mice. In these mice UV-induced immunosuppression was prevented. Pilot studies by Kripke et al. indicated that the release of IL-IO and TNF alpha that are both induced by DNA damage might be involved. In preliminary studies with mice that were deficient with respect to DNA repair lower doses of UV were needed for the induction of immunosuppression as compared to their normal littermates. These studies indicate that altered gene expression plays a pivotal role in UVB-induced immunosuppression. In addition to a role for UCA and DNA in UV-induced immunosuppression it is postulated recently that signal transduction (EGF-receptor mediated upregulation of phospholipase A2) and transcription factors (NF kappa B, p91) are involved in UV-induced immunomodulation.
Authors:
J Garssen; R J Vandebriel; H van Loveren
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Archives of toxicology. Supplement. = Archiv für Toxikologie. Supplement     Volume:  19     ISSN:  0171-9750     ISO Abbreviation:  Arch. Toxicol. Suppl.     Publication Date:  1997  
Date Detail:
Created Date:  1997-06-12     Completed Date:  1997-06-12     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  7802567     Medline TA:  Arch Toxicol Suppl     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  97-109     Citation Subset:  IM    
Affiliation:
Laboratory for Pathology and Immunobiology, National Institute of Public health and the Environment, Bilthoven, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA Damage*
Down-Regulation
Gene Expression / radiation effects*
Immune System / physiology,  radiation effects*
Mice
Pyrimidine Dimers / physiology
Skin / chemistry,  radiation effects
Ultraviolet Rays / adverse effects*
Urocanic Acid / radiation effects
Chemical
Reg. No./Substance:
0/Pyrimidine Dimers; 104-98-3/Urocanic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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