Linked Life Data

17082642

Source:http://linkedlifedata.com/resource/pubmed/id/17082642

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-11-3
pubmed:abstractText
Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation. This involves cellular migration across various structures associated with the blood-brain barrier: the vascular endothelium, the glia limitans, and the perivascular space between them. Leukocytes accumulate spontaneously in the perivascular space in brains of transgenic (Tg) mice that overexpress CCL2 under control of a CNS-specific promoter. The Tg mice show no clinical symptoms, even though leukocytes have crossed the endothelial basement membrane. Pertussis toxin (PTx) given i.p. induced encephalopathy and weight loss in Tg mice. We used flow cytometry, ultra-small superparamagnetic iron oxide-enhanced magnetic resonance imaging, and immunofluorescent staining to show that encephalopathy involved leukocyte migration across the glia limitans into the brain parenchyma, identifying this as the critical step in inducing clinical symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor of metalloproteinase-1, metalloproteinase disintegrins-12, MMP-8, and -10 in brains of Tg mice. Levels of the microglial-associated MP MMP-15 were not affected in control or PTx-treated Tg mice. PTx also up-regulated expression of proinflammatory cytokines IL-1beta and TNF-alpha mRNA in Tg CNS. Weight loss and parenchymal infiltration, but not perivascular accumulation, were significantly inhibited by the broad-spectrum MP inhibitor BB-94/Batimastat. Our finding that MPs mediate PTx-induced parenchymal infiltration to the chemokine-overexpressing CNS has relevance for the pathogenesis of human diseases involving CNS inflammation, such as multiple sclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7242-9
pubmed:meshHeading
pubmed-meshheading:17082642-Animals, pubmed-meshheading:17082642-Brain, pubmed-meshheading:17082642-Brain Diseases, pubmed-meshheading:17082642-Cell Movement, pubmed-meshheading:17082642-Central Nervous System, pubmed-meshheading:17082642-Chemokine CCL2, pubmed-meshheading:17082642-Cytokines, pubmed-meshheading:17082642-Female, pubmed-meshheading:17082642-Gene Expression Regulation, pubmed-meshheading:17082642-Inflammation Mediators, pubmed-meshheading:17082642-Injections, Intraperitoneal, pubmed-meshheading:17082642-Male, pubmed-meshheading:17082642-Metalloproteases, pubmed-meshheading:17082642-Mice, pubmed-meshheading:17082642-Mice, Inbred C57BL, pubmed-meshheading:17082642-Mice, Transgenic, pubmed-meshheading:17082642-Pertussis Toxin, pubmed-meshheading:17082642-Phenylalanine, pubmed-meshheading:17082642-Thiophenes, pubmed-meshheading:17082642-Weight Loss
pubmed:year
2006
pubmed:articleTitle
Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system.
pubmed:affiliation
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't