The antipsoriatic dimethyl-fumarate suppresses interferon-gamma -induced ICAM-1 and HLA-DR expression on...

The derivatives of fumaric acid show antipsoriatic effects but details of the mechanism of action are largely unknown. The study focused on the effect of fumaric acid, dimethyl-fumarate, Zn-, Ca- and Mg-monoethyl-fumarate on the interferon-gamma (IFN-gamma)-induced expression of ICAM-1 and HLA-DR molecules on keratinocytes. Human hyperproliferative keratinocytes of the HaCaT cell line were exposed to IFN-gamma (10 U/ml) alone or in combination with fumaric acid and its derivatives for 48 hrs. The effect of fumarates was investigated semiquantitatively using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method. Subsequently, the effect of dimethyl-fumarate, the main component of "fumaric acid therapy", was evaluated quantitatively by means of an APAAP-ELISA technique. The semiquantitative evaluation revealed that in the micromolar dose range investigated only dimethyl-fumarate demonstrated substantial growth inhibition and down-regulation of the cell surface markers. In the quantitative evaluation, dimethyl-fumarate significantly (p