Linked Life Data

11223159

Source:http://linkedlifedata.com/resource/pubmed/id/11223159

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-3-6
pubmed:abstractText
RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemoattractant activity for T lymphocytes and monocytes/macrophages that are implicated in the pathogenesis of multiple sclerosis (MS) lesions. Glatiramer acetate is a drug recently approved for the treatment of MS. We therefore investigated the effect of glatiramer acetate on RANTES expression in glial cells in vitro. Treatment of human U-251 MG astroglial cells with glatiramer acetate blocks IL-1beta-induced RANTES chemokine production in a dose- and time-dependent manner. Glatiramer acetate also decreased steady-state levels of RANTES mRNA in these cells, which was attributable to reduced transcription, as assessed by nuclear run-on assays. In addition, we showed that NF-kappaB may be the transcriptional activator responsible for the IL-1beta-mediated RANTES gene expression in this system. Our data indicated that the IL-1beta-induced increase in RANTES was associated with an increase in in vitro nuclear extract binding activity specific for the NF-kappaB site in the promoter region of the RANTES gene. The increases in RANTES mRNA and protein expression were suppressed by the NF-kappaB inhibitors gliotoxin, isohelenin, and pyrrolidine dithiocarbamate (PDTC). Furthermore, we demonstrated that the increase in NF-kappaB DNA-binding activity was prevented by pretreatment with glatiramer acetate or the NF-kappaB inhibitors. Our results suggest that glatiramer acetate may inhibit IL-1beta-stimulated RANTES expression in human glial cells by blocking NF-kappaB activation, thus identifying part of the molecular basis for its anti-inflammatory and immunosuppressive effects in demyelinating diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-60
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11223159-Astrocytes, pubmed-meshheading:11223159-Astrocytoma, pubmed-meshheading:11223159-Brain Neoplasms, pubmed-meshheading:11223159-Chemokine CCL5, pubmed-meshheading:11223159-Demyelinating Autoimmune Diseases, CNS, pubmed-meshheading:11223159-Gene Expression Regulation, pubmed-meshheading:11223159-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:11223159-Humans, pubmed-meshheading:11223159-Immunosuppressive Agents, pubmed-meshheading:11223159-Interleukin-1, pubmed-meshheading:11223159-Interleukin-6, pubmed-meshheading:11223159-Interleukin-8, pubmed-meshheading:11223159-NF-kappa B, pubmed-meshheading:11223159-Peptides, pubmed-meshheading:11223159-RNA, Messenger, pubmed-meshheading:11223159-Transcription, Genetic, pubmed-meshheading:11223159-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Glatiramer acetate blocks interleukin-1-dependent nuclear factor-kappaB activation and RANTES expression in human U-251 MG astroglial cells.
pubmed:affiliation
Departments of Neurology, University of Maryland School of Medicine, 21201, Baltimore, MD, USA. qli001@umaryland.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.