Inflammation resolved by retinoid X receptor‐mediated inactivation of leukotriene signaling pathways
| Autor: | Henry W. Strobel, Madeleine Duvic, Ying Wang, Liping Du, Auinash Kalsotra, Patricia A. Ladd, Alan S. Boyd, Yasushi Kikuta, Diane S. Keeney |
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| Rok vydání: | 2007 |
| Předmět: |
Leukotrienes
medicine.drug_class Leukotriene B4 Tretinoin Inflammation Retinoid X receptor Biochemistry Gene Expression Regulation Enzymologic chemistry.chemical_compound Cytochrome P-450 Enzyme System Genetics medicine Humans Retinoid Molecular Biology Cells Cultured Leukotriene Retinoid X receptor alpha Chemistry Cell Differentiation Retinoid X receptor gamma Up-Regulation Retinoid X Receptors Epidermal Cells Immunology Cancer research Epidermis Retinoid X receptor beta medicine.symptom Signal Transduction Biotechnology |
| Zdroj: | The FASEB Journal. 22:538-547 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.07-9244com |
| Popis: | Leukotrienes are implicated in the pathogenesis of diverse, inflammation-driven diseases. Metabolic inactivation of leukotriene signaling is an innate response to resolve inflammation, yet little is known of mechanisms regulating disposition of leukotrienes in peripheral tissues afflicted in common inflammatory diseases. We studied leukotriene hydroxylases (CYP4F gene products) in human skin, a common target of inflammation and adverse drug reactions. Epidermal keratinocytes express at least six CYP4F enzymes; the most highly expressed and highly regulated is CYP4F3A-the main neutrophil leukotriene hydroxylase. Differentiation-specific factors and retinoids are positive CYP4F regulators in vitro, effecting increased leukotriene B4 hydroxylation (inactivation). CYP4F expression is up-regulated in situ in hyperproliferative dermatoses-an innate mechanism to repair and restore epidermal barrier competency-and after retinoid therapy. Enhanced CYP4F-mediated inactivation of leukotriene signaling is a previously unrecognized antiinflammatory property of therapeutic retinoids mediated by preferential interactions between retinoid X receptors and CYP4F promoter elements in epidermal cells. |
| Databáze: | OpenAIRE |
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