| FTY720 attenuates accumulation of EMAP-II+ and MHC-II+ monocytes in early lesions of rat traumatic brain injury. | |
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MedLine Citation:
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PMID: 17488479 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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FTY720 (Fingolimod) is a novel type of immunosuppressive agent inhibiting lymphocyte egress from secondary lymphoid tissues thereby causing peripheral lymphopenia. FTY720 can inhibit macrophage infiltration into inflammatory lesions under pathological conditions. FTY720 has been clinically evaluated for prophylaxis of allograft rejection and treatment of multiple sclerosis, showing promising immunosuppressive effects. A robust inflammatory response after traumatic brain injury (TBI) plays an important role in the secondary or delayed injuries of TBI. Here we have investigated by immunohistochemistry in a rat TBI model the effects of FTY720 on early cell accumulation into the inflammatory tissue response and on expression of major histo-compatibility complex class II (MHC-II) and endothelial-monocyte activating polypeptide II (EMAP-II). Accumulation of MHC-II(+) or EMAP-II(+) cells became significant 1 day after injury and continuously increased during the early time periods. Further, double-staining experiments confirmed that the major cellular sources of MHC-II were reactive macrophages, however MHC-II(+) cells only constituted a small subpopulation of reactive macrophages. Immediately after TBI, peripheral administration of FTY720 (1 mg/kg in 1 mL saline, every second day) significantly attenuated the accumulation of MHC-II(+) macrophages from Day 1 to 4 and significantly attenuated the accumulation of EMAP-II(+) macrophages/microglia at Day 4. Our findings show that FTY720 attenuates early accumulation of EMAP-II(+) and MHC-II(+) reactive monocytes following TBI, indicating that FTY720 might be a drug candidate to inhibit brain inflammatory reaction following TBI. |
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Authors:
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Zhiyuan Zhang; Zhiren Zhang; Uwe Fauser; Matthias Artelt; Michael Burnet; Hermann J Schluesener |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cellular and molecular medicine Volume: 11 ISSN: 1582-1838 ISO Abbreviation: J. Cell. Mol. Med. Publication Date: 2007 Mar-Apr |
Date Detail:
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Created Date: 2007-05-09 Completed Date: 2007-07-17 Revised Date: 2008-06-05 |
Medline Journal Info:
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Nlm Unique ID: 101083777 Medline TA: J Cell Mol Med Country: Romania |
Other Details:
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Languages: eng Pagination: 307-14 Citation Subset: IM |
Affiliation:
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Institute of Brain Research, University of Tuebingen, Calwer Strasse 3, D-72076 Tuebingen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Injuries / etiology, pathology* Cytokines / biosynthesis* Histocompatibility Antigens Class II / metabolism* Immunohistochemistry Immunosuppressive Agents / pharmacology* Monocytes / physiology* Neoplasm Proteins / biosynthesis* Propylene Glycols / pharmacology* RNA-Binding Proteins / biosynthesis* Rats Rats, Inbred Lew Sphingosine / analogs & derivatives*, pharmacology Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Histocompatibility Antigens Class II; 0/Immunosuppressive Agents; 0/Neoplasm Proteins; 0/Propylene Glycols; 0/RNA-Binding Proteins; 0/small inducible cytokine subfamily E, member 1; 123-78-4/Sphingosine; 162359-55-9/fingolimod |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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