Dimethylfumarate induces apoptosis in human mast cells. Issue 11 (29th October 2013)

• Record Type: Journal Article
• Authors: Förster, Anja; Preussner, Liane M.; Seeger, Jens M.; Rabenhorst, Anja; Kashkar, Hamid; Mrowietz, Ulrich; Hartmann, Karin
• Is Part Of: Experimental dermatology. Volume 22:Issue 11(2013:Nov.)
• Page Start: 719
• Page End: 724
• Publication Date: 2013-10-29
• Subjects: apoptosis -- dimethylfumarate -- fumaric acid esters -- mast cells -- psoriasis; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.12247
• Languages: English
• ISSNs: 0906-6705

Abstract

Abstract: Mast cells modulate autoimmune diseases such as psoriasis and multiple sclerosis. Fumaric acid esters (FAEs) are widely used for the treatment of psoriasis, and dimethylfumarate (DMF) has recently been approved for multiple sclerosis. In this study, we analysed the cytotoxic effect of FAEs on human mast cells. Specifically, cell death was analysed in the human mast cell line HMC‐1 and in primary cord blood‐derived mast cells (CBMCs) after incubation with fumaric acid (FA), monomethylfumarate (MMF), DMF and calcium bis(monomethylfumarate) (Ca‐MF). Our data show that only DMF potently induces apoptotic cell death in HMC‐1 cells and CBMCs. DMF‐mediated apoptosis was associated with increased expression of Bax and Bak and activation of caspase‐9 and caspase‐6. Interestingly, DMF also enhanced the sensitivity of CBMCs towards TRAIL‐ and dexamethasone‐induced apoptosis. These findings demonstrate for the first time that DMF induces apoptosis of human mast cells, primarily via the mitochondrial apoptotic pathway. Our study contributes to the understanding of the beneficial effects of FAEs in autoimmune diseases and provides a rationale for exploiting FAEs for other diseases associated with mast cells.