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Imprint
Identification of Nrf2-target genes in human THP-1 monocytes 2009: Identification of Nrf2 target genes in human THP-1 monocytes upon treatment with contact allergens by means of proteomic analysis 2010: Identification of Nrf2 target genes in human THP-1 monocytes upon treatment with contact allergens by means of proteomic analysis
Project
Project code: BfR-TOX-08-1322-350
Contract period: 01.04.2008
- 31.12.2010
Purpose of research: Applied research
This study is to identify detoxifying enzymes or proteasomal components in THP-1 mono-cytes that are regulated by the transcription factor Nrf2. The induction of expression of such proteins may indicate a cellular stress response, e.g. upon exposure to sensitizing agents. Cells that are stably expressing RNAi against Nrf2-RNA down-regulating Nrf2 (RNAi-gene knock down) may not react adequately by the upregulation of detoxifying proteins upon ex-posure to sensitizers. We intend to compare protein expression in wildtype versus Nrf2 defi-cient human THP-1 cells that are both stimulated with the contact sensitizer cinnamal in order to identify novel metabolically relevant proteins in cells able to present antigens.2009:Today, a variety of chemical induced allergies are well known, including skin sensiti-zation resulting in allergic contact dermatitis. Chemical allergens are low molecular weight compounds that cannot induce an immune response by their own. They act as haptens, and for immune activation usually covalent binding to proteins is re-quired. This occurs after internalization into epidermal Langerhans cells (LC). The sensitizing potency of a chemical thus depends on the metabolism in LC, which is not studied in detail so far. Some chemicals will be detoxified and excreted while others will be activated and converted into protein-reactive species. The transcription factor Nrf2 has a key role in protecting cells against oxidative or chemical induced stress. In cell culture experiments we want to analyze whether treatment with con-tact allergens may lead to changes in the cellular proteom mediated via Nrf2. In ad-dition, we want to comparatively investigate the effects of non-sensitizing but irritat-ing chemicals. For proteomic analyses we will also apply Nrf2-deficient THP-1 cells that are sup-posed to metabolize allergens in a different way.
Section overview
Subjects
- Toxicology
Framework programme
Funding programme
Excutive institution
BfR - Department 9: Experimental Toxicology and ZEBET (BfR - TOX)
