Source:http://linkedlifedata.com/resource/pubmed/id/10462039
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
1999-9-2
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| pubmed:abstractText |
Perivascular leukocyte infiltration into the central nervous system is characteristic of multiple sclerosis (MS) pathology. Interferon-beta (IFN-beta) has shown efficacy in the treatment of patients with MS, but the relevant mechanisms remain incompletely understood. In this study the effects of IFN-beta on leukocyte transendothelial migration were investigated using cells relevant to MS pathogenesis, namely human brain microvascular endothelial cells (HB-MVEC). Activated, but not resting leukocytes exhibited a high transendothelial migration capacity. HB-MVEC prestimulated with tumor necrosis factor (TNF) and IFN-gamma significantly promoted leukocyte transendothelial migration. IFN-beta inhibited the activated leukocyte transendothelial migration on TNF/IFN-gamma-activated HB-MVEC in a dose-dependent manner. A matrix metalloproteinase (MMP) inhibitor and monoclonal antibodies to lymphocyte function antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1), but not to very late antigen-4 or to vascular cell adhesion molecule-1 significantly inhibited the transendothelial migration of stimulated leukocytes, suggesting that this phenomenon involves the LFA-1/ICAM-1 interaction and MMP. However IFN-beta did not interfere with the binding of leukocytes to HB-MVEC unless IFN-beta was preincubated with leukocytes or added to HB-MVEC at the time of stimulation. Furthermore IFN-beta did not modulate the expression of adhesion molecules on either stimulated leukocytes or activated HB-MVEC, but partially reduced TNF and interleukin-1 production from stimulated leukocytes during coculture with HB-MVEC. Interestingly, in the presence of IFN-beta, a significant down-regulation of MMP-9 release from stimulated leukocytes was found, especially for the activated form of MMP-9. These results indicate that inhibition of leukocyte transendothelial migration is an important mechanism accounting for the beneficial effects of IFN-beta in the treatment MS patients.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagenases,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lymphocyte Homing,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
|
| pubmed:issn |
0023-6837
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
79
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1015-25
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:10462039-Brain,
pubmed-meshheading:10462039-Cell Adhesion,
pubmed-meshheading:10462039-Cell Movement,
pubmed-meshheading:10462039-Cells, Cultured,
pubmed-meshheading:10462039-Collagenases,
pubmed-meshheading:10462039-Endothelium, Vascular,
pubmed-meshheading:10462039-Humans,
pubmed-meshheading:10462039-Integrin alpha4beta1,
pubmed-meshheading:10462039-Integrins,
pubmed-meshheading:10462039-Intercellular Adhesion Molecule-1,
pubmed-meshheading:10462039-Interferon-beta,
pubmed-meshheading:10462039-Interferon-gamma,
pubmed-meshheading:10462039-Interleukin-1,
pubmed-meshheading:10462039-Leukocytes,
pubmed-meshheading:10462039-Matrix Metalloproteinase 9,
pubmed-meshheading:10462039-Microcirculation,
pubmed-meshheading:10462039-Multiple Sclerosis,
pubmed-meshheading:10462039-Receptors, Lymphocyte Homing,
pubmed-meshheading:10462039-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10462039-Vascular Cell Adhesion Molecule-1
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| pubmed:year |
1999
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| pubmed:articleTitle |
Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer.
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| pubmed:affiliation |
Department of Anesthesiology, Pharmacology and Surgical Intensive Care, University Medical Center, Geneva, Switzerland.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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