Source:http://linkedlifedata.com/resource/pubmed/id/19561616
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
2009-7-8
|
| pubmed:abstractText |
Previous proteomic and transcriptional analyses of multiple sclerosis lesions revealed modulation of the renin-angiotensin and the opposing kallikrein-kinin pathways. Here we identify kinin receptor B1 (Bdkrb1) as a specific modulator of immune cell entry into the central nervous system (CNS). We demonstrate that the Bdkrb1 agonist R838 (Sar-[D-Phe]des-Arg(9)-bradykinin) markedly decreases the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in SJL mice, whereas the Bdkrb1 antagonist R715 (Ac-Lys-[D-betaNal(7), Ile(8)]des-Arg(9)-bradykinin) resulted in earlier onset and greater severity of the disease. Bdkrb1-deficient (Bdkrb1(-/-)) C57BL/6 mice immunized with a myelin oligodendrocyte glycoprotein fragment, MOG(35-55), showed more severe disease with enhanced CNS-immune cell infiltration. The same held true for mixed bone marrow-chimeric mice reconstituted with Bdkrb1(-/-) T lymphocytes, which showed enhanced T helper type 17 (T(H)17) cell invasion into the CNS. Pharmacological modulation of Bdkrb1 revealed that in vitro migration of human T(H)17 lymphocytes across blood-brain barrier endothelium is regulated by this receptor. Taken together, these results suggest that the kallikrein-kinin system is involved in the regulation of CNS inflammation, limiting encephalitogenic T lymphocyte infiltration into the CNS, and provide evidence that Bdkrb1 could be a new target for the treatment of chronic inflammatory diseases such as multiple sclerosis.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
1546-170X
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| pubmed:author |
pubmed-author:AktasOrhanO,
pubmed-author:BaderMichaelM,
pubmed-author:BendixIvoI,
pubmed-author:HanMay HtweMH,
pubmed-author:HerzJosephineJ,
pubmed-author:IferganIgalI,
pubmed-author:MoriMarcelo AMA,
pubmed-author:PaterkaMagdalenaM,
pubmed-author:PratAlexandreA,
pubmed-author:ProzorovskiTimourT,
pubmed-author:SchadockInesI,
pubmed-author:SchröterFriederikeF,
pubmed-author:Schulze-TopphoffUlfU,
pubmed-author:SiffrinVolkerV,
pubmed-author:SmorodchenkoAlinaA,
pubmed-author:SteinmanLawrenceL,
pubmed-author:Van HorssenJackJ,
pubmed-author:ZippFraukeF
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
15
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
788-93
|
| pubmed:dateRevised |
2011-11-4
|
| pubmed:meshHeading |
pubmed-meshheading:19561616-Animals,
pubmed-meshheading:19561616-Brain,
pubmed-meshheading:19561616-Cell Movement,
pubmed-meshheading:19561616-Encephalomyelitis, Autoimmune, Experimental,
pubmed-meshheading:19561616-Interleukin-17,
pubmed-meshheading:19561616-Mice,
pubmed-meshheading:19561616-Mice, Inbred C57BL,
pubmed-meshheading:19561616-Receptor, Bradykinin B1,
pubmed-meshheading:19561616-T-Lymphocytes,
pubmed-meshheading:19561616-Th1 Cells
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system.
|
| pubmed:affiliation |
Cecilie Vogt Klinik, Charité-University Hospital Berlin, Max Delbrueck Center for Molecular Medicine and NeuroCure Research Center, Berlin, Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|