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Health effects of UVB exposure with special emphasis on infectious in man.

Objetivo

The objectives of the present proposal are to study the relationship between dose, wavelength and duration of UVB exposure and the effect on resistance to infections. The proposed studies will further advance knowledge with respect to mechanisms controlling adaptation, immunological tolerance and susceptibility of humans and animals. This information is necessary to improve the risk estimation for effects of UVB on the resistances to infections. Using mathematical models describing relationships between different parameters of the immune system and resistance to infections, animal data will be extrapolated to the human situation. The project will also investigate whether available epidemiological data on relevant infections in man are suitable for validation of the mathematically calculated (extrapolated) data.

* Immune system
The target cells, i.e. keratinocytes, LCs, fibroblasts, T cells, mast cells, NK cells, PMNLs will be studied with
respect to UV-effects in different species. The effects, i.e. altered release or production of mediators or altered
expression of surface markers will be studied. Both in vivo and in vitro exposure experiments are necessary.
Additionally, the role of urocanic acid (UCA) and DNA will be examined with respect to their roles as initiators
of UVB-induced immunosuppression.
* Infections
1. Skin-associated infections. Responsible triggers for recurrent herpes simplex (HSV) infections in man and
animal will be further analyzed: both genotoxic and immunotoxic phenomena may play a role. Tools to analyse
these triggers are in vivo and ex vivo/in vitro specific immune responses to the pathogen in animals and man.
For special purposes, transgenic animal models will be used (i.e. cytokine deficient, DNA repair deficient, UCA
deficient). Immune responses studied are functional activity of lymphocytes, keratinocytes, LCs. In vivo
readout systems are pathogen detection, contact and delayed-type hypersensitivity, immunopathology, antibody
production. Ex vivo/in vitro read out systems used are: cytokines, adhesion molecules, major histocompatibility
complex antigens, lymphocyte proliferation, cytotoxic T cell activity. Skin-associated infections that will be
investigated include HSV and varicella zoster virus (VZV).
2. Non-skin-associated infections. By relating climatology data (sunshine, UVB exposure, etc.) from the last
20 years with data dealing with the incidence of infectious diseases in humans, it may be possible to analyze
the effect of UVB exposure on the incidence and severity of infectious diseases. Non-skin-associated infections
that will be investigated in animals include those caused by cytomegalovirus, murine gammaherpes virus (similar
to human UVB), Trichinella spiralis, influenza, and Listeria monocytogenes.
* Genotoxicity
In man and mice expression of p53, as well as the frequency of p53 mutations, will be studied and related to
UVB induced immunosuppression. Two transgenic mouse strains that are deficient either with respect to DNA
repair or to p53 dependent apoptosis, will be used as tools to investigate whether DNA damage is important for
the effects on the resistance to infections.
* Risk-analysis
Animal models and reserach in humans will be performed to select biomarkers that can be used to comprehend
mechansms controlling adaptation, tolerance and sysceptibility, which are necessary for a solid risk assessment.
All the data obtained by the different participants will be further described in quantitative terms in a
mathematical model, and be integrated for a better risk-estimation. Epidemiology will be applied for validation
of the analysis.

Convocatoria de propuestas

Data not available

Régimen de financiación

CSC - Cost-sharing contracts

Coordinador

Rijksinstituut voor Volksgezondheid en Milieuhygiëne
Aportación de la UE
Sin datos
Dirección
9,Antonie van Leeuwenhoeklaan
3720 BA Bilthoven
Países Bajos

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Coste total
Sin datos

Participantes (5)