Linked Life Data

11509646

Source:http://linkedlifedata.com/resource/pubmed/id/11509646

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-8-17
pubmed:abstractText
Chemokines are small chemotactic cytokines that modulate leukocyte recruitment and activation during inflammation. Here, we describe the role of macrophage inflammatory protein-1alpha (MIP-1alpha) during cuprizone intoxication, a model where demyelination of the CNS features a large accumulation of microglia/macrophage without T cell involvement or blood-brain barrier disruption. RNase protection assays showed that mRNA for numerous chemokines were up-regulated during cuprizone treatment in wild-type, C57BL/6 mice. RANTES, inflammatory protein-10, and monocyte chemoattractant protein-1 showed greatest expression with initiation of insult at 1-2 wk of treatment, whereas MIP-1alpha and beta increased later at 4-5 wk, coincident with peak demyelination and cellular accumulation. The function of MIP-1alpha during demyelination was tested in vivo by exposing MIP-1alpha knockout mice (MIP-1alpha(-/-)) to cuprizone and comparing pathology to wild-type mice. Demyelination at 3.5 wk of treatment was significantly decreased in MIP-1alpha(-/-) mice ( approximately 36% reduction), a result confirmed by morphology at the electron microscopic level. The delay in demyelination was correlated to apparent decreases in microglia/macrophage and astrocyte accumulation and in TNF-alpha protein levels. It was possible that larger effects of the MIP-1alpha deficiency were being masked by other redundant chemokines. Indeed, RNase protection assays revealed increased expression of several chemokine transcripts in both untreated and cuprizone-treated MIP-1alpha(-/-) mice. Nonetheless, despite this possible compensation, our studies show the importance of MIP-1alpha in demyelination in the CNS and highlight its effect, particularly on cellular recruitment and cytokine regulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2964-71
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11509646-Animals, pubmed-meshheading:11509646-Astrocytes, pubmed-meshheading:11509646-Blood-Brain Barrier, pubmed-meshheading:11509646-Chemokine CCL3, pubmed-meshheading:11509646-Chemokine CCL4, pubmed-meshheading:11509646-Chemokine CCL5, pubmed-meshheading:11509646-Chemokines, pubmed-meshheading:11509646-Cuprizone, pubmed-meshheading:11509646-Demyelinating Autoimmune Diseases, CNS, pubmed-meshheading:11509646-Macrophage Inflammatory Proteins, pubmed-meshheading:11509646-Macrophages, pubmed-meshheading:11509646-Male, pubmed-meshheading:11509646-Mice, pubmed-meshheading:11509646-Mice, Inbred C57BL, pubmed-meshheading:11509646-Mice, Knockout, pubmed-meshheading:11509646-Microglia, pubmed-meshheading:11509646-RNA, Messenger, pubmed-meshheading:11509646-Receptors, Chemokine, pubmed-meshheading:11509646-Tumor Necrosis Factor-alpha, pubmed-meshheading:11509646-Up-Regulation
pubmed:year
2001
pubmed:articleTitle
Absence of macrophage-inflammatory protein-1alpha delays central nervous system demyelination in the presence of an intact blood-brain barrier.
pubmed:affiliation
Department of Microbiology and Immunology, University of North Carolina-Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't