Universität zu Köln

Foerster, Anja, Preussner, Liane M., Seeger, Jens M., Rabenhorst, Anja, Kashkar, Hamid, Mrowietz, Ulrich and Hartmann, Karin ORCID: 0000-0002-4595-8226 (2013). Dimethylfumarate induces apoptosis in human mast cells. Exp. Dermatol., 22 (11). S. 719 - 725. HOBOKEN: WILEY. ISSN 1600-0625

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Foerster, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Preussner, Liane M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeger, Jens M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rabenhorst, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED Mrowietz, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Karin UNSPECIFIED orcid.org/0000-0002-4595-8226 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-472217
DOI:	10.1111/exd.12247
Journal or Publication Title:	Exp. Dermatol.
Volume:	22
Number:	11
Page Range:	S. 719 - 725
Date:	2013
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-0625
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FUMARIC-ACID ESTERS; PLACEBO-CONTROLLED PHASE-3; MULTIPLE-SCLEROSIS; ORAL BG-12; PSORIASIS; LINE; INHIBITION; EXPRESSION; RELEASE; DISEASE Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47221