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- Andresen Bergström, Moa,1978Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry (author)
A skin-like cytochrome P450 cocktail activates prohaptens to contact allergenic metabolites.
- Article/chapterEnglish2007
Publisher, publication year, extent ...
- Elsevier BV,2007
Numbers
- LIBRIS-ID:oai:gup.ub.gu.se/54618
- https://gup.ub.gu.se/publication/54618URI
- https://doi.org/10.1038/sj.jid.5700638DOI
Supplementary language notes
- Language:English
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Notes
- Allergic contact dermatitis is a complex syndrome representing immunological responses to cutaneous exposure to protein-reactive chemicals. Although many contact sensitizers directly can elicit this disorder, others (prohaptens) require activation. Knowledge regarding the activating mechanisms remains limited, but one possibility is metabolic activation by cytochrome P450 (CYP) enzymes in the skin. We have, after quantitative reverse transcriptase-PCR studies of the CYP content in 18 human skin samples, developed an enriched skin-like recombinant human (rh) CYP cocktail using CYP1A1, 1B1, 2B6, 2E1, and 3A5. To validate the rhCYP cocktail, a prohaptenic conjugated diene ((5R)-5-isopropenyl-2-methyl-1-methylene-2-cyclohexene) was investigated using: the skin-like rhCYP cocktail, a liver-like rhCYP cocktail, single rhCYP enzymes, liver microsomes, keratinocytes, and a dendritic cell (DC) assay. The diene was activated to sensitizing epoxides in all non-cell-based incubations including the skin-like rhCYP cocktail. An exocyclic epoxide metabolite ((7R)-7-isopropenyl-4-methyl-1-oxaspiro[2.5]oct-4-ene) was found to be mainly responsible for the allergenic activity of the diene. This epoxide also induced pronounced DC activation indicated by upregulation of IL-8. The skin-like rhCYP cocktail provides a simplified alternative to using skin tissue preparations in mechanistic studies of CYP-mediated skin metabolism of prohaptens and offers the future possibility of designing in vitro predictive assays for assessment of allergenic activity of prohaptens.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Läkemedelskemi hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Medicinal Chemistry hsv//eng
- Allergens
- immunology
- metabolism
- Animals
- Biotransformation
- physiology
- Cells
- Cultured
- Cytochrome P-450 Enzyme System
- physiology
- Dendritic Cells
- cytology
- metabolism
- Dermatitis
- Allergic Contact
- immunology
- metabolism
- Female
- Haptens
- immunology
- metabolism
- Humans
- Interleukin-8
- genetics
- metabolism
- Keratinocytes
- cytology
- metabolism
- Male
- Mice
- Mice
- Inbred Strains
- Microsomes
- Liver
- enzymology
- RNA
- Messenger
- genetics
- metabolism
- Skin
- enzymology
- immunology
- Up-Regulation
Added entries (persons, corporate bodies, meetings, titles ...)
- Ott, Hagen (author)
- Carlsson, AnnaGothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry (author)
- Neis, Mark (author)
- Zwadlo-Klarwasser, Gabriele (author)
- Jonsson, Charlotte A,1971Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry(Swepub:gu)xjonch (author)
- Merk, Hans F (author)
- Karlberg, Ann-Therese,1947Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry(Swepub:gu)xkaann (author)
- Baron, Jens M (author)
- Göteborgs universitetInstitutionen för kemi (creator_code:org_t)
Related titles
- In:The Journal of investigative dermatology: Elsevier BV127:5, s. 1145-531523-17470022-202X
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