Dimethylfumarate induces apoptosis in human mast cells

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.

Dimethyl fumarate modulates neutrophil extracellular trap formation in a glutathione‐ and superoxide‐dependent manner

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Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway

“…DMF was reported to induce cell apoptosis in human mast cells (Forster et al ., ). Since DMF reduced the viability of SGC‐7901, HT29, HCT116 and CT26 cells, we further investigated whether the reduced cell viability was due to the induction of apoptosis in HCT116 and CT26 cells by measuring different apoptosis‐related factors, bcl‐2, bax, caspase‐3, in these cells after DMF treatment.…”

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

“…While no evidence for specific mast cell targeted agents in the treatment of MS was detected in the literature, it was noted that a recent drug that was approved for treatment of the remitting-relapsing form of the disease, dimethyl fumarate (discussed in [ 69 ]), was shown to induce mast cell apoptosis in vitro [ 70 ]. Of the multiple variants of the drug, only the dimethyl fumarate form was effective in inducing apoptosis of human HMC-1 cells and cord blood derived-mast cells.…”