Dimethylfumarate Inhibits Tumor-Necrosis-Factor-Induced CD62E Expression in an NF-κB-Dependent Manner
| Autor: | Wolfgang Wiegrebe, Manuela Pillinger, Robert Loewe, Ulrich Mrowietz, Peter Petzelbauer, Klaus Wolff, Wolfgang Holnthoner, David Jirovsky, Rainer de Martin, Marion Gröger |
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| Rok vydání: | 2001 |
| Předmět: |
Umbilical Veins
Fumaric acid Dimethyl Fumarate medicine.medical_treatment Gene Expression Dermatology Biology Biochemistry Umbilical vein chemistry.chemical_compound Fumarates In vivo medicine Humans RNA Messenger Molecular Biology Cells Cultured Skin Tumor Necrosis Factor-alpha NF-kappa B psoriasis Cell Biology Intercellular Adhesion Molecule-1 Molecular biology endothelial cells methylhydrogenfumarate In vitro Capillaries Endothelial stem cell medicine.anatomical_structure Cytokine chemistry fumaric acid esters CD54 Tumor necrosis factor alpha Dermatologic Agents Endothelium Vascular E-Selectin Keratinocyte |
| Zdroj: | Journal of Investigative Dermatology. 117:1363-1368 |
| ISSN: | 0022-202X |
| Popis: | Fumaric acid esters are thought to improve psoriasis by altering leukocyte, keratinocyte, and/or endothelial functions. To determine specificity, kinetics, and molecular mechanisms of different fumaric acid esters in their ability to inhibit endothelial cell activation, we analyzed CD62E and CD54 expression in endothelial cells in vivo and in vitro. In lesional skin of psoriatic patients, oral fumaric acid ester treatment resulted in a marked reduction of CD62E but not CD54 expression on dermal microvessels. Using human umbilical vein endothelial cells, dimethylfumarate almost completely inhibited tumor-necrosis-factor-induced CD62E, but not CD54 expression at concentrationsor = 70 microM, mimicking the situation in vivo. A 60 min dimethylfumarate preincubation was sufficient to block tumor-necrosis-factor-induced CD62E expression for up to 24 h. In contrast, equimolar concentrations of methylhydrogenfumarate, the hydrolysis product of dimethylfumarate, did not suppress tumor-necrosis-factor-induced CD62E expression. Likewise, all fumaric acid esters other than dimethylfumarate were ineffective. Using CD62E, NF-kappa B, or AP-1-responsive promoter constructs, dimethylfumarate inhibited tumor-necrosis-factor-induced activation of the CD62E and the NF-kappa B but not the AP-1 promoter construct. In summary, at a dose rangeor = 70 microM, dimethylfumarate appeared to be a specific inhibitor of CD62E expression in an NF-kappa B-dependent manner. |
| Databáze: | OpenAIRE |
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