Loewe, Robert and Pillinger, Manuela and de Martin, Rainer and Mrowietz, Ulrich and Groeger, Marion and Holnthoner, Wolfgang and Wolff, Klaus and Wiegrebe, Wolfgang and Jirovsky, David and Petzelbauer, Peter (2001) Dimethylfumarate inhibits tumor-necrosis-factor-induced CD62E expression in an NF-kappa B-dependent manner. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 117 (6). pp. 1363-1368. ISSN 0022-202X
Full text not available from this repository. (Request a copy)Abstract
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 concentrations less than or equal to 70 muM, 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-kappaB, or AP-1-responsive promoter constructs, dimethylfumarate inhibited tumor-necrosis-factor-induced activation of the CD62E and the NF-kappaB but not the AP-1 promoter construct. In summary, at a dose range less than or equal to 70 muM, dimethylfumarate appeared to be a specific inhibitor of CD62E expression in an NF-kappaB-dependent manner.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FUMARIC-ACID DERIVATIVES; INDUCED E-SELECTIN; FACTOR-ALPHA; ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; PSORIASIS; MONOMETHYLFUMARATE; TRANSCRIPTION; MULTICENTER; NEUTROPHILS; CD54; endothelial cells; fumaric acid esters; methylhydrogenfumarate; psoriasis |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Nov 2021 06:44 |
| Last Modified: | 24 Nov 2021 06:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40906 |
Actions (login required)
 |
View Item |
