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Characterization of cellular effects of contact sensitizers in vitro: Analysis of phosphotyrosine signaling pathways by far western blotting and establishment of a screening method
Project
Project code: BfR-PRS-08-1322-457
Contract period: 01.04.2010
- 31.12.2010
Purpose of research: Applied research
A range of low molecular weight chemicals can induce allergic contact dermatitis. In the development of allergic contact dermatitis two phases can be separated: sensitization and elicitation. During sensitization contact allergens or sensitizers penetrate through the skin barrier and interact with epidermal dendritic cells (Langerhans cells), which then may become activated and will migrate toward regional lymph nodes to induce T cell-mediated immune responses. In order to pass the Stratum corneum most sensitizers are hydrophobic. Sensitizers itself act only as haptens and for activation of dendritic cells they need to attach covalenty to proteins. Thus most sensitizers are electrophiles. In general, however, sensitizers rather share only few, if any common structural features.Evaluation of the sensitizing potency of chemicals still relies on animal testing, mostly in the so-called local lymph node assay. In terms of cosmetics and due to the 7th amendment of the cosmetics directive, animal testing will be banned by 2013. Therefore, there is a great demand to develop alternative methods for the testing of toxicological propterties of chemicals. Currently there are several promising approaches but most of them are still not validated and accepted or got stuck at the R&D stage. Most likely a combination of several in vitro assays will need to be combined, each of which addressing different molecular aspects in compound-mediated contact allergy.In the present project our focus will be on the more global analysis of signal transduction pathways induced in cells upon treatment with sensitizers. In pilot experiments we could demonstrate that chemical sensitizers significantly increase phospho-tyrosine-levels in those cells exposed. This effect possibly can be linked to oxidative stress, commonly occurring in cells in response to contact sensitizers.The intracellular levels of phospho-tyrosine can be analyzed with the aid of so-called SH2 domains.
Section overview
Subjects
- Biotechnology
