دورية أكاديمية
Topical application of fingolimod perturbs cutaneous inflammation
| العنوان: | Topical application of fingolimod perturbs cutaneous inflammation |
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| المؤلفون: | Sun, W.Y., Dimasi, D.P., Pitman, M.R., Zhuang, Y., Heddle, R., Pitson, S.M., Grimbaldeston, M.A., Bonder, C.S. |
| المصدر: | http://dx.doi.org/10.4049/jimmunol.1501510Test. |
| بيانات النشر: | American Association of Immunologists |
| سنة النشر: | 2016 |
| المجموعة: | The University of Adelaide: Digital Library |
| مصطلحات موضوعية: | Neutrophils, Cells, Cultured, Skin, Animals, Mice, Inbred C57BL, Knockout, Humans, Multiple Sclerosis, Dermatitis, Disease Models, Animal, Histamine, Phosphotransferases (Alcohol Group Acceptor), Immunoglobulin E, Inflammation Mediators, Cytokines, Administration, Topical, Cell Movement, Capillary Permeability, Fingolimod Hydrochloride |
| الوصف: | The prevalence of allergies, including rhinitis, eczema, and anaphylaxis, is rising dramatically worldwide. This increase is especially problematic in children who bear the greatest burden of this rising trend. Increasing evidence identifies neutrophils as primary perpetrators of the more severe and difficult to manage forms of inflammation. A newly recognized mechanism by which neutrophils are recruited during the early phase of histamine-induced inflammation involves the sphingosine kinase (SK)/sphingosine-1-phosphate axis. This study examines whether topical application of fingolimod, an established SK/sphingosine-1-phosphate antagonist already in clinical use to treat multiple sclerosis, may be repurposed to treat cutaneous inflammation. Using two mouse models of ear skin inflammation (histamine- and IgE-mediated passive cutaneous anaphylaxis) we topically applied fingolimod prophylactically, as well as after establishment of the inflammatory response, and examined ear swelling, SK activity, vascular permeability, leukocyte recruitment, and production of proinflammatory mediators. The present study reveals that when applied topically, fingolimod attenuates both immediate and late-phase responses to histamine with reduced extravasation of fluid, SK-1 activity, proinflammatory cytokine and chemokine production, and neutrophil influx and prevents ear swelling. Intravital microscopy demonstrates that histamine-induced neutrophil rolling and adhesion to the postcapillary venules in the mouse ears is significantly attenuated even after 24 h. More importantly, these effects are achievable even once inflammation is established. Translation into humans was also accomplished with epicutaneous application of fingolimod resolving histamine-induced and allergen-induced inflammatory reactions in forearm skin. Overall, this study demonstrates, to our knowledge for the first time, that fingolimod may be repurposed to treat cutaneous inflammation. ; Wai Y. Sun, David P. Dimasi, Melissa R. Pitman, YiZhong Zhuang, Robert ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-1767 1550-6606 |
| العلاقة: | Journal of Immunology, 2016; 196(9):3854-3864; http://hdl.handle.net/2440/100144Test; Pitman, M.R. [0000-0002-9587-3837]; Zhuang, Y. [0000-0003-2083-964X]; Pitson, S.M. [0000-0002-9527-2740]; Bonder, C.S. [0000-0001-9875-967X] |
| DOI: | 10.4049/jimmunol.1501510 |
| الإتاحة: | https://doi.org/10.4049/jimmunol.1501510Test http://hdl.handle.net/2440/100144Test |
| حقوق: | Copyright © 2016 by The American Association of Immunologists, Inc. |
| رقم الانضمام: | edsbas.F8A7D4A |
| قاعدة البيانات: | BASE |
| تدمد: | 00221767 15506606 |
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| DOI: | 10.4049/jimmunol.1501510 |