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Home Search Quick Search Advanced Fulltext Browse Collections Persons My eDoc Session History Login Name: Password: Documentation Help Support Wiki Direct access to document ID:	Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents ID: 711917.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015 Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate's protective effect in EAE Authors: Chen, H.; Assmann, J. C.; Krenz, A.; Rahman, M.; Grimm, M.; Karsten, C. M.; Kohl, J.; Offermanns, S.; Wettschureck, N.; Schwaninger, M. Date of Publication (YYYY-MM-DD): 2014-05 Title of Journal: J Clin Invest Volume: 124 Issue / Number: 5 Start Page: 2188 End Page: 2192 Audience: Not Specified Abstract / Description: Taken orally, the drug dimethyl fumarate (DMF) has been shown to improve functional outcomes for patients with MS; however, it is unclear how DMF mediates a protective effect. DMF and, more so, its active metabolite, monomethyl fumarate, are known agonists of the hydroxycarboxylic acid receptor 2 (HCA(2)), a G protein-coupled membrane receptor. Here, we evaluated the contribution of HCA(2) in mediating the protective effect afforded by DMF in EAE, a mouse model of MS. DMF treatment reduced neurological deficit, immune cell infiltration, and demyelination of the spinal cords in wild-type mice, but not in Hca2(-)/(-) mice, indicating that HCA(2) is required for the therapeutic effect of DMF. In particular, DMF decreased the number of infiltrating neutrophils in a HCA(2)-dependent manner, likely by interfering with neutrophil adhesion to endothelial cells and chemotaxis. Together, our data indicate that HCA(2) mediates the therapeutic effects of DMF in EAE. Furthermore, identification of HCA(2) as a molecular target may help to optimize MS therapy. Free Keywords: Animals; Cell Adhesion/drug effects/genetics; *Encephalomyelitis, Autoimmune, Experimental/drug; therapy/genetics/metabolism/pathology; Female; Fumarates/*pharmacology; Humans; Immunosuppressive Agents/*pharmacology; Mice; Mice, Knockout; Multiple Sclerosis/drug therapy/genetics/metabolism/pathology; Neutrophil Infiltration/*drug effects; Neutrophils/*metabolism/pathology; Receptors, G-Protein-Coupled/genetics/*metabolism; Receptors, Nicotinic/genetics/*metabolism External Publication Status: published Document Type: Article Communicated by: MPI für Herz- und Lungenforschung Affiliations: MPI für physiologische und klinische Forschung Identifiers: ISSN:1558-8238 (Electronic) 0021-9738 (Linking) %R 10.1172/JCI72151 URL:http://www.ncbi.nlm.nih.gov/pubmed/24691444 %^ 143... The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.