Differentiation-Specific Factors Modulate Epidermal CYP1–4 Gene Expression in Human Skin in Response to Retinoic Acid and Classic Aryl Hydrocarbon Receptor Ligands
| Autor: | Diane S. Keeney, Liping Du, Patricia A. Ladd, Mark M. Neis |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Keratinocytes
Male Polychlorinated Dibenzodioxins Cellular differentiation Blotting Western Retinoic acid Tretinoin Gene Expression Regulation Enzymologic chemistry.chemical_compound Cytochrome P-450 Enzyme System Downregulation and upregulation Gene expression medicine Humans RNA Messenger Skin Pharmacology Regulation of gene expression biology Reverse Transcriptase Polymerase Chain Reaction Infant Newborn Cell Differentiation Aryl hydrocarbon receptor Molecular biology Up-Regulation Transcription Factor AP-1 Cross-Linking Reagents medicine.anatomical_structure Receptors Aryl Hydrocarbon chemistry CYP2S1 biology.protein Molecular Medicine Factor XIIIa Keratinocyte |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 319:1162-1171 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Human epidermal keratinocytes express subsets of cytochromes P450 (P450) (CYP gene products) that are strongly up-regulated, not regulated, or down-regulated by differentiation-specific factors. We investigated how drug exposure affects epidermal expression of CYP1-4 genes, which encode many drug-metabolizing P450s. Real-time polymerase chain reaction (PCR) assays measured CYP1-4 mRNA levels in epidermal keratinocytes differentiated in vitro in the presence of drug or vehicle for 6 days. We confirmed the spinous phenotype at day 6 by changes in cellular morphology and upregulation of cytokeratin 10 and transglutaminase (TGM)1 mRNA in the differentiating keratinocytes. Effects of drug exposure depended on the influence of differentiation-specific factors in controlling epidermal CYP1-4 expression. CYP2C18, 2C19, 2C9, 2W1, 3A4, and 4B1 are up-regulated by cellular differentiation; mRNA levels for these CYP genes were inhibited in differentiating keratinocytes exposed to retinoic acid and aryl hydrocarbon receptor (AhR) ligands. These same drugs effected |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|