Dimethylfumarate is an inhibitor of cytokine-induced E-selectin, VCAM-1, and ICAM-1 expression in human endothelial cells.
Most studies on the antipsoriatic mode of action of dimethylfumarate focused on its antiproliferative effects in keratinocytes. Because inflammatory skin diseases are associated with an upregulation of endothelial cell adhesion molecules and because the presence of inflammatory cells in dermis and epidermis is considered an important feature in psoriasis, we tested the effect of DMF on cytokine-induced adhesion molecule expression in HUVEC, using in situ ELISA and Northern blotting. Dimethylfumarate inhibited ICAM-1, VCAM-1, and E-selectin expression and reduced adhesion of U937 cells to stimulated HUVEC. Monoethylfumarate and fumaric acid had no effect. Similar inhibitory effects for DMF on VCAM-1 expression were observed after stimulation of HUVEC with LPS, PMA, IL-4, and IL-1 alpha or in combinations with TNF alpha. These data are in agreement with previously reported effects of DMF on intracellular thiol levels and inhibition of NF-kappa B activation. The inhibitory effect on cytokine-induced endothelial adhesion molecule expression may represent another target of dimethylfumarate in psoriasis.
Vandermeeren
M
M
Department for Cell Biology and Developmental Genetics, Janssen Research Foundation, Beerse, Belgium.
Janssens
S
S
Borgers
M
M
Geysen
J
J
D015152:Blotting, Northern; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology*; D000069462:Dimethyl Fumarate; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005650:Fumarates / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007378:Interleukins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011565:Psoriasis / Q000188:drug therapy; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014470:Umbilical Cord; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D005650:Fumarates; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C032005:fumaric acid; D000069462:Dimethyl Fumarate; D013755:Tetradecanoylphorbol Acetate; C061175:ethyl fumarate