Dimethylfumarate Reduces Leukocyte Rolling in Vivo through Modulation of Adhesion Molecule Expression
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| Název: | Dimethylfumarate Reduces Leukocyte Rolling in Vivo through Modulation of Adhesion Molecule Expression |
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| Autoři: | Rubant, Simone A., Ludwig, Ralf J., Diehl, Sandra, Hardt, Katja, Kaufmann, Roland, Pfeilschifter, Josef M., Boehncke, Wolf-Henning |
| Zdroj: | Journal of Investigative Dermatology, Vol. 128, No 2 (2008) pp. 326-331 |
| Informace o vydavateli: | Elsevier BV, 2008. |
| Rok vydání: | 2008 |
| Témata: | Male, Fumarates/*pharmacology, Dimethyl Fumarate, Bacterial Toxins, E-Selectin/genetics/metabolism, Down-Regulation, Cell Adhesion Molecules/genetics/*metabolism, Dermatology, In Vitro Techniques, Immunosuppressive Agents/*pharmacology, Biochemistry, Enterotoxins, Mice, 03 medical and health sciences, 0302 clinical medicine, Fumarates, Cell Adhesion, Animals, Humans, Leukocyte Rolling, Molecular Biology, Enterotoxins/pharmacology, Leukocyte Rolling/*drug effects/physiology, Cells, Cultured, Mice, Knockout, Leukocytes, Mononuclear/cytology, Bacterial Toxins/pharmacology, Venules/cytology, P-Selectin/genetics/metabolism, Cell Biology, Mice, Inbred C57BL, P-Selectin, Solubility, Down-Regulation/drug effects/immunology, Vascular Cell Adhesion Molecule-1/genetics/metabolism, Leukocytes, Mononuclear, Cell Adhesion/*drug effects/immunology, E-Selectin, Cell Adhesion Molecules, Superantigens/pharmacology, Immunosuppressive Agents |
| Popis: | 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. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 0022-202X |
| DOI: | 10.1038/sj.jid.5700996 |
| Přístupová URL adresa: | http://www.jidonline.org/article/S0022202X15337106/pdf https://pubmed.ncbi.nlm.nih.gov/17671516 https://www.sciencedirect.com/science/article/abs/pii/S0022202X15337106 http://www.nature.com/jid/journal/v128/n2/full/5700996a.html https://pubmed.ncbi.nlm.nih.gov/17671516/ https://www.jidonline.org/article/S0022-202X(15)33710-6/fulltext https://www.ncbi.nlm.nih.gov/pubmed/17671516 https://archive-ouverte.unige.ch/unige:29882 https://archive-ouverte.unige.ch/unige:29882 |
| Rights: | Elsevier Non-Commercial |
| Přístupové číslo: | edsair.doi.dedup.....3000a637071aa6996732dd2bd684f18b |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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. |
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| ISSN: | 0022202X |
| DOI: | 10.1038/sj.jid.5700996 |