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Dimethylfumarate Reduces Leukocyte Rolling in Vivo through Modulation of Adhesion Molecule Expression
- Source :
- Journal of Investigative Dermatology, Vol. 128, No 2 (2008) pp. 326-331
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Esters of fumaric acid have a long tradition in the treatment of psoriasis. Dimethylfumarate (DMF) is perceived as the main active substance. However, the molecular mechanisms of DMF action are not completely understood. Here, we investigate the effects of DMF on lymphocyte adhesion molecule expression in vitro and interactions with endothelial cells in vivo. DMF dose-dependently reduced superantigen-induced expression of CD25, human leukocyte antigen-DR, and cutaneous lymphocyte antigen by 27, 22, and 48% on CD3-positive cells, respectively. No change was observed for CD54, VLA-4, and P-selectin glycoprotein ligand-1. An enhancement of CD69 expression was noted (22%). DMF led to a significant reduction in binding of human peripheral blood mononuclear cells (PBMCs) to E-selectin (72%), P-selectin (36%), and vascular cell adhesion molecule-1 (33%) in vitro. Intravital microscopy of PBMCs in ear vasculature of wild-type and knockout mice showed that rolling was mainly P-selectin-dependent and could be reduced by 61% through DMF incubation. We provide early evidence that DMF affects adhesion molecule expression on human leukocytes and their rolling behavior in vivo, indicating that DMF directly affects the initial step of leukocyte extravasation.
- Subjects :
- Male
Fumarates/*pharmacology
Dimethyl Fumarate
Lymphocyte
Biochemistry
Enterotoxins
Mice
chemistry.chemical_compound
Fumarates
Venules
Cells, Cultured
Enterotoxins/pharmacology
Mice, Knockout
Leukocytes, Mononuclear/cytology
Superantigens
Dimethyl fumarate
Chemistry
Cell adhesion molecule
Leukocyte extravasation
P-Selectin
medicine.anatomical_structure
Down-Regulation/drug effects/immunology
Cell Adhesion/*drug effects/immunology
E-Selectin
Immunosuppressive Agents
Superantigens/pharmacology
Intravital microscopy
Bacterial Toxins
E-Selectin/genetics/metabolism
Down-Regulation
Vascular Cell Adhesion Molecule-1
Cell Adhesion Molecules/genetics/*metabolism
Leukocyte Rolling
Dermatology
In Vitro Techniques
Immunosuppressive Agents/*pharmacology
In vivo
Cell Adhesion
medicine
Animals
Humans
Cell adhesion
Molecular Biology
Leukocyte Rolling/*drug effects/physiology
Bacterial Toxins/pharmacology
Venules/cytology
P-Selectin/genetics/metabolism
Cell Biology
Molecular biology
Mice, Inbred C57BL
Solubility
Immunology
Leukocytes, Mononuclear
Vascular Cell Adhesion Molecule-1/genetics/metabolism
Cell Adhesion Molecules
Subjects
Details
- ISSN :
- 0022202X
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....3000a637071aa6996732dd2bd684f18b